IDENTIFICATION OF SENV GENOTYPES

Abstract: The present invention relates to a nucleic acid molecule representing the genome of a virus/viral agent, said nucleic acid molecule having at least one of the following features: (a) it contains at least one open reading frame (ORF) which encodes a polypeptide having an amino acid sequence disclosed herein; (b) it comprises a DNA sequence as described herein; (c) it hybridizes preferably under stringent conditions to the complementary strand of the nucleic acid molecule described herein, but not to the complementary strand of the genome of TT virus; (d) it is degenerate with respect to the hybridizing nucleic acid molecule; (e) it is at least 60 % identical with the nucleic acid molecule representing the genome of the virus/viral agent of the invention; and (f) parts of it can be amplified under suitable conditions by PCR employing primers as defined herein. The invention further relates to vectors comprising said nucleic acid molecule, methods of producing (poly)peptide(s) encoded by said nucleic acid molecule, to viruses/viral agents carrying a genome represented by said nucleic acid molecule and antibodies to said (poly)peptide(s) and/or said viruses/viral agents. Additionally, the invention relates to compositions, preferably pharmaceutical compositions, vaccines, diagnostics and diagnostic kits comprising or employing the compounds of the invention.

Description: Identification of SENV Genotypes A number of documents are cited in this specification. The contents of all the documents is hereby incorporated by reference. The present invention relates to a nucleic acid molecule representing the genome of a virus/viral agent, said nucleic acid molecule having at least one of the following features: (a) it contains at least one open reading frame (ORF) which encodes a polypeptide having an amino acid sequence disclosed herein, (b) it comprises a DNA sequence as described herein; (c) it hybridizes preferably under stringent conditions to the complementary strand of the nucleic acid molecule described herein, but not to the complementary strand of the genome of TT virus; (d) it is degenerate with respect to the hybridizing nucleic acid molecule; (e) it is at least 60% identical with the nucleic acid molecule representing the genome of the virus/viral agent of the invention; and (f) parts of it can be amplified under suitable conditions by PCR employing primers as defined herein. The invention further relates to vectors comprising said nucleic acid molecule, methods of producing (poly)peptide(s) encoded by said nucleic acid molecule, to viruses/viral agents carrying a genome represented by said nucleic acid molecule and antibodies to said (poly)peptide(s) and/or said viruses/viral agents. Additionally, the invention relates to compositions, preferably pharmaceutical compositions, vaccines, diagnostics and diagnostic kits comprising or employing the compounds of the invention. Since the early 1980s, more and more viral agents have been described, which are parenterally transmitted (for example, HIV, Hepatitis G virus, TT Virus, etc.), but a direct causal relationship between distinct diseases and those viruses has often not been established. One of these diseases is hepatitis. This hepatopathy is one of the most important diseases transmitted from donor to recipient by transfusion or other administration of blood products, by organ transplantation or haemodialysis. Hepatitis is also transmitted via ingestion of contaminated water or nutrition and can be community- acquired (person-to-person contact). Viral agents suspected of causing such hepatopathies include hepatitis A-(HAV), hepatitis B- (HBV), hepatitis C- (HCV), hepatitis D- (HDV), hepatitis E- (HEV) or, hepatitis G-virus (HGV/HGBV-C) as well as cytomegalovirus (CMV) and Epstein-Barr virus (EBV). Although sensitive and specific tests for detection of known hepatitis viruses are available, the etiology of a substantial fraction of post-transfusion (Alter et al., W. Eng. J. Med. 321 (1989), 1494) and community-acquired hepatitis (Alter et al., N. Engl. J. Med. 327 (1989), 1899) is unknown. A number of potential pathogens have been proposed as aetiogenic agents for these so-called non-A, non-B, non-C, non-D, non-E, non-G hepatopathies (reviewed or described in Prince, Annu. Rev. Microbiol. 37 (1983) 217; Feinstone and Hoofnagle, N. Engl. J. Med. 311 (1984), 185; Overby, Curr. Hepatol. 7 (1987), 35; Iwarson, British Medical J. 295 (1987), 949; Alter et al., N. Engl. J. Med. 336 (1997) 747). However, proof that these viral agents are the causative pathogens for these hepatic disorders is missing, especially since most patients with fulminant hepatitis do not show markers of hepatitis virus infection (Feray et al., Gastroenterology 104 (1993), 549; Wright, Gastroenterology 104 (1993), 640). This is because patients with chronic liver disease are reported who appear not to be infected with known hepatitis viruses from A to E (Kodali et al., Am. J. Gastroenterol. 89 (1994), 1836; NANE hepatitis). Further post-transfusion hepatitis occurs in about 10% of transfused patients, whereas hepatitis of unknown etiological origin accounts for up to 90% of these cases. Especially the discovery of hepatitis C virus (HCV) made it apparent that a proportion of cases with acute and chronic hepatitis are still negative for all known viral markers (Alter et al., Semi. Liver Dis 15 (1995), 110-120) which prompted investigations to search for new hepatitis causing agents. Since then, a substantial effort has continued in the search for other infectious agents responsible for residual cases of post-transfusion non-A/non-B hepatitis not caused by HCV, of cryptogenic fulminant hepatic failure (FHF) and of chronic hepatitis. Furthermore, recent findings indicate that infection with hepatitis G virus (HGV/HGBV-C; WO 95/21922), although widespread, is not an etiological agent in the majority of the above clinical presentations of hepatitis (Alter, N. Engl. J. Med. 334 (1996), 1536-1537; Alter et al., N. Engl. J. Med. 336 (1997), 747-754). In 1997, investigators in Japan isolated a DNA clone of a novel human virus, designated TTV, using a representation-difference analysis from serum samples from a patient ("patient TT"; also called "transfusion transmitted virus"; see Nishizawa et al., Biochem. Biophys. Res. Commun. 241 (1997), 92-97) with post-transfusion hepatitis of unknown etiology. Preliminary data show that TTV is an unenveloped, single-stranded DNA virus with 3739 nucleotides (Okamoto, et al., Hepatology Res. 10 (1998), 1-16). Two genetic groups of this virus have been identified, differing by 30% in nucleotide sequences. TTV DNA was detected in 47% of patients with fulminant non-A-G hepatitis and 46% of patients with chronic liver diseases of unknown etiology, suggesting that TTV may be the cause of some cryptogenic liver diseases. More recent findings however have casted doubt on the potential pathogenicity of TTV. Naumov et al. (Lancet 352 (1998), 159-197) have demonstrated that TTV (Alter, N. Engl. J. Med. 334 (1996), 1536-1537; Alter et al., N. Engl. J. Med. 336 (1997), 747- 754) is present in the UK with a similar prevalence and the same viral genotypes as in Japan, suggesting that TTV has a worldwide distribution. However, the majority of TTV-positive cases had normal liver-function tests and only minor changes in liver histology. The high prevalence of TTV infection in the general population both in the UK and Japan and the lack of significant hepatopathies suggested that TTV, similar to hepatitis G-virus (HGV), may be a virus without clear disease association. The rate of TTV infection in the normal, healthy population is at least three times higher than the prevalence of HGV agent in the general population which appear to be 1.7% in the USA (Linnen et al., Science 271 (1996), 505-508) and 3.2% in Scotland (Jarvis et al., Lancet 348 (1996), 1352-1355). Although the majority of patients with TTV infection had a history of blood transfusion or intravenous drug use, confirming the importance of the parenteral route of transmission, the agent is also detected in a large proportion of individuals with "community-acquired" infection (38%). Therefore, a likely non-parenteral transmission of TTV requires further investigation. Although Naumov et al. (loc. cit.) showed that the prevalence of TTV infection was slightly higher in liver-disease patients with non-B, non-C etiology than in healthy controls, this result does not necessarily imply a causative role of TTV as hepatopathy inducing agent, since the majority of TTV-positive cases had normal liver-function tests and only minor changes in liver histology. These data suggest, that TTV is not the causative agent of chronic liver diseases of unknown etiology. Furthermore, it seems as if TTV does not affect the degree of liver damage after coinfection with HBV or HCV. Thus, the scenario for TTV seems to be similar to that for the HGB virus C/HGV since the clinical implication of infection with this agent is increasingly doubtful. In 73% of cases, HGV infections were not accompanied by hepatocellular injury, and an additional 16% were associated with only a minor rise in alanine aminotransferase (Alter, N. Engl. J. Med. 334 (1996), 1536-1537; Alter et al., N. Engl. J. Med. 336 (1997), 747-754). Therefore, the findings that TTV has no apparent pathogenic role for liver diseases is another example of a human virus that has no clear disease association. In 1999 it was concluded by Matsumoto et al. (Matsumoto et al., Hepatology 30 (1999), 283-288) that TTV is a very common, often persistent infection that is transmitted by transfusion and by undefined nosocomial routes. However, no association between TTV and non-A to E hepatitis was found and these authors could not detect an effect of TTV on the severity or duration of coexisting hepatitis C. It was concluded that TTV may not be a primary hepatitis virus. Since the causative, etioiogical agent(s), which are parenterally transmitted and can be the pathogens leading to the above described hepatopathies or other diseases of unknown origin in transfusion patients or intravenous drug users are not known, the technical problem underlying the present invention was thus to provide for novel agents, which are implied in, associated with or responsible for the development of such hepatopathies or other diseases. The solution to said technical problem is achieved by providing the embodiments characterized in the claims. Accordingly, the present invention relates to a nucleic acid molecule representing the genome of a virus/viral agent, said nucleic acid molecule having at least one of the following features: (a) it contains at least one ORF which encodes a polypeptide having the amino acid sequence of (aa) SEQ ID NO: 21 , SEQ ID NO: 25, SEQ ID NO: 27, SEQ ID NO: 29, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 80, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 91 , SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 180, SEQ ID NO: 182, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198 or of (ab) SEQ ID NO: 81 , SEQ ID NO: 122, SEQ ID NO: 181 , SEQ ID NO: 188; (b) it comprises the DNA sequence of SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 20, SEQ ID NO: 24, SEQ ID NO: 26, SEQ ID NO: 28, SEQ ID NO: 30, SEQ ID NO: 31 , SEQ ID NO: 34, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51 , SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 94, SEQ ID NO: 95 SEQ ID NO: 96, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121 , SEQ ID NO: 125, SEQ ID NO: 177, SEQ ID NO: 179, SEQ ID NO: 183, SEQ ID NO: 184, SEQ ID NO: 185, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 191 , SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201 or SEQ ID NO: 202; (c) it comprises portions of at least 80 nucleotides, preferably at least 100 nucleotides, more preferably at least 500 nucleotides and most preferably at least 2000 nucleotides which hybridize (under stringent conditions) to the complementary strand of the nucleic acid molecule of SEQ ID NO: 26, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 125, SEQ ID NO: 186, SEQ ID NO: 191 , SEQ ID NO: 199; (d) it is degenerate with respect to the nucleic acid molecule of (c) but does not hybridize to the complementary strand of the genome of TT virus; (e) it is at least 50%, preferably at least 60% and more preferably at least 70% identical with the nucleic acid molecule of SEQ ID NO: 26, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 125 or SEQ ID NO: 186, SEQ ID NO: 191 , SEQ ID NO: 199, at least 60%, preferably at least 70% and more preferably at least 80% identical with the nucleic acid molecule of SEQ ID NO: 24, SEQ ID NO: 34, SEQ ID NO: 75, SEQ ID NO: 87, SEQ ID NO: 118 or SEQ ID NO: 179, SEQ ID NO: 187, SEQ ID NO: 195, it contains an ORF or a fragment thereof which is at least 50%, preferably at least 60% and more preferably at least 75% identical with the nucleic acid molecule of SEQ ID NO: 28, SEQ ID NO: 39, SEQ ID NO: 89, SEQ ID NO: 184 or SEQ ID NO: 193, at least 60%, preferably at least 70% and more preferably at least 75% identical with the nucleic acid molecule of SEQ ID NO: 77, SEQ ID NO: 120, SEQ ID NO: 177 or SEQ ID NO: 201 , at least 50%, preferably at least 60% and more preferably at least 75% identical with the nucleic acid molecule of SEQ ID NO: 30, SEQ ID NO: 40, SEQ ID NO: 78, SEQ ID NO: 90, EQ ID NO: 121S, SEQ ID NO: 185, SEQ ID NO: 194 or SEQ ID NO: 202, at least 50%, preferably at least 60% and more preferably at least 75% identical with the nucleic acid molecule of SEQ ID NO: 79 or at least 50%, preferably at least 60% and more preferably at least 75% identical with the nucleic acid molecule of SEQ ID NO: 31 , SEQ ID NO: 38, SEQ ID NO: 76, SEQ ID NO: 88, SEQ ID NO: 119, SEQ ID NO: 183, SEQ ID NO: 192 or SEQ ID NO: 200 or it is a nucleic acid molecule comprising a nucleic acid molecule encoding an amino acid sequence which is at least 35%, preferably at least 40%, more preferably at least 50% and most preferably at least 75% identical with SEQ ID NO: 21 , SEQ ID NO: 25 SEQ ID NO: 27, SEQ ID NO: 29, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61 , SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 80, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 91 , SEQ ID NO: 92, SEQ ID NO: 93 or SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 180, SEQ ID NO: 182, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 196, SEQ ID NO: 197 or SEQ ID NO: 198 or it is a nucleic acid molecule encoding an amino acid sequence which is at least 40%, preferably at least 50% and most preferably at least 75% identical with SEQ ID NO: 81 , SEQ ID NO: 122, SEQ ID NO: 181 or SEQ ID NO: 188; (f) parts of it can be amplified under suitable conditions by PCR employing as primers oligonucleotides as defined in SEQ ID NO: 41 and SEQ ID NO: 42 and/or as defined in SEQ ID NO: 115 and SEQ ID NO: 71 or as defined in SEQ ID NO: 11 , SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 32, SEQ ID NO: 73, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101 , SEQ ID NO: 102, SEQ ID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128; SEQ ID NO: 129, SEQ ID NO: 130, SEQ ID NO: 131 , SEQ ID NO: 132, SEQ ID NO: 135, SEQ ID NO: 136, SEQ ID NO: 172, SEQ ID NO: 173, SEQ ID NO: 174, SEQ ID NO: 175, SEQ ID NO: 176 or SEQ ID NO: 203, SEQ ID NO: 204 or SEQ ID NO: 205 or the complementary strand of such an oligonucleotide; and (g) it deviates from any one of the above molecules by insertion, substitution, inversion, deletion, duplication, recombination, addition or a combination thereof. In the context of the present invention, the term "genome" defines not only sequences which are open reading frames (ORFs) encoding proteins, polypeptides or peptides, but also refers to non-coding sequences. Accordingly, the term "nucleic acid molecule" comprises coding and, wherever applicable, non-coding sequences. The nucleic acid molecule of the invention furthermore comprises nucleic acid sequences which are degenerative to the above nucleic acid sequences. In accordance with the present invention, the term "nucleic acid molecule" comprises also any feasible derivative of a nucleic acid to which a nucleic acid probe may hybridize. Said nucleic acid probe itself may be a derivative of a nucleic acid molecule capable of hybridizing to said nucleic acid molecule or said derivative thereof. The term "nucleic acid molecule" further comprises peptide nucleic acids (PNAs) containing DNA analogs with amide backbone linkages (Nielsen, P., Science 254 (1991), 1497-1500). The term "ORF" ("open reading frame") which encodes a (preferably expressed) polypeptide, in connection with the present invention, is defined either by (a) the specific nucleotide sequences encoding the polypeptides specified above in (aa) or in (ab) or (b) by nucleic acid sequences hybridizing under stringent conditions to the complementary strand of the nucleotide sequences of (a) and encoding a polypeptide deviating from the polypeptide of (a) by one or more amino acid substitutions, deletions, duplications, insertions, recombinations, additions or inversions and wherein the amino acid sequence shows at least 35% identity with the amino acid sequence of said polypeptide of (aa) or encoding a polypeptide deviating from the polypeptide of (a) by one or more amino acid substitutions, deletions or inversions and wherein the amino acid sequence shows at least 40% identity with the amino acid sequence of said polypeptide of (ab). Thus, the nucleic acid molecule comprised by the nucleic acid molecules in (e), supra, would also be considered as ORFs. Preferably, the nucleic acid molecule representing the genome of a virus as defined herein is the nucleic acid molecule representing the genome of a pathogenic virus. The term "pathogenic virus" as used herein means a virus which is capable of a viral pathogenesis, wherein said pathogenesis is defined as the method by which said virus/viral agent produces or contributes to disease in a host. The term pathogenesis refers herein to acute as well as/or to chronic infections as they occur in humans or other hosts. Pathogenesis therefore means the mechanism by which said virus injures discrete populations of cells in different organs or an organ to produce the signs and symptoms of disease of a host. Said diseases comprise, inter alia, hepatopathologies, like hepatitis or hepatocarcinomas. Furthermore, the term "pathogentic virus" means in accordance with the invention a virus/viral agent which is capable of negatively influencing the physiological state of a host even without primariiy causing distinct signs and/or symptoms of disease. Therefore, the term "pathogenic virus" also refers to a virus/viral agent which aggravates a clinical condition in a host, e.g., after or during infection with another pathogenic organism (secondary or co-infection after viral, bacterial, fungal, protozoal and/or helminthic infections) or in weakened, immunocompromised hosts/patients. Consequently, the term "pathogenic virus" not only comprises viruses/viral agents which are capable of causing a primary infection but also compπses viruses/viral agents which cause secondary infections. Additionally, the term "pathogenic virus" means a virus/viral agent which causes or contributes directly to a disease or disease symptoms in a host but also comprises viruses/viral agents which are indirectly involved in pathological processes in a patient. The term "pathogenic virus" in context of this invention, therefore, compπses viruses/viral agents which have a direct disease association, aggravate a (even pre-existing) clinical condition in a host/patient and/or are indirectly involved in a pathological condition of a host/patient. The term "hybridizes" as used in accordance with the present invention may relate to stringent or non-stringent conditions. If not further specified, the conditions are preferably non-stringent. Said hybridization conditions may be established according to conventional protocols described, for example, in Sambrook, "Molecular Cloning, A Laboratory Manual", Cold Spring Harbor Laboratory, N.Y. (1989), Ausubel, "Current Protocols in Molecular Biology", Green Publishing Associates and Wiley Interscience, N.Y. (1989), or Higgins and Hames (Eds) "Nucleic acid hybridization, a practical approach" IRL Press Oxford, Washington DC, (1985). The setting of conditions is well within the skill of the artisan and to be determined according to protocols described in the art. Thus, the detection of only specifically hybridizing sequences will usually require stringent hybridization and washing conditions such as O.lxSSC, 0.1% SDS at 65°. Non-stringent hybridization conditions for the detection of homologous or not exactly complementary sequences may be set at 6xSSC, 1% SDS at 65°C. As is well known, the length of the probe and the composition of the nucleic acid to be determined constitute further parameters of the hybridization conditions. Hybridizing nucleic acid molecules or molecules falling under alternative (c), supra, also comprise fragments of the molecules identified in (a), or (b) wherein the nucleotide sequence need not be identical to its counterpart in SEQ ID NOs: 2, 4, 5, 6, 8, 9, 14, 15, 16, 17, 20, 24, 26, 28, 30, 31 , 34, 38, 39, 40, 43, 44, 45, 46, 47, 48, 49, 50, 51 , 52, 53, 54, 55, 56, 75, 76, 77, 78, 79, 87, 88, 89, 90, 94, 95, 96, 116, 117, 118, 119, 120, 121 , 125, 177, 179, 183, 184, 185, 186, 187, 191 , 192, 193, 194, 195, 199, 200, 201 or 202 said fragments representing the genome or parts of the genome of a virus, and having a length of at least 12 nucleotides, preferably at least 15, more preferably at least 18, more preferably of at least 21 nucleotides, more preferably at least 30 nucleotides, even more preferably at least 40 nucleotides and most preferably at least 60 nucleotides. Furthermore, nucleic acid molecules which hybridize with any of the aforementioned nucleic acid molecules also include fragments, derivatives and allelic variants of these molecules. The term "derivative" means in this context that the nucleotide sequence of these nucleic acid molecules differs from the sequences of the above-described nucleic acid molecules in one or more nucleotide positions and they are highly homologous to said nucleic acid molecules. Additionally or alternatively, the term "derivative" means a compound that does not or not solely consist of DNA, PNA or RNA as well as any chemically or biologically modified nucleic acid. Homology is understood to refer in the context of "fragments", "derivatives" or "allelic variants" to a sequence identity of at least 55%, particularly an identity of at least 70%, preferably more than 80% and still more preferably more than 90%. Generally, nucleotide or amino acid sequence identities/homologies can be determined conventionally by using known computer programs such as BLASTIN, BLASTP, NALIGN or PALIGN using particular algorithms to find the best segment of homology between two segments. In the context of the present invention the comparative analysis of the percentage of identities at the amino acid level of the different ORFs are preferably obtained using the PALIGN program of the PCGENE package (Intelligenetics) using the following parameters: Open Gap Cost: 10 and Unit Gap Cost: 2. Furthermore, in the context of the present invention comparative analysis of the percentage of identities at the nucleotide level of the different nucleic acid sequences, on the other hand, are preferably obtained using the NALIGN program of the PCGENE package using the following parameters: Open Gap Cost: 100 and Unit Gap Cost: 10. It was found that these parameters are the best suited to calculate the percentage of identity over the full length of the reference nucleotide or amino acid sequences, especially considering the different levels of homology among the different sequences analyzed. The deviations from the sequences of the nucleic acid molecules described above can, for example, be the result of nucleotide substitution(s), deletion(s), addition(s), insertion(s) duplicatron(s), inversion(s) and/or recombination(s) either alone or in combination, that may naturally occur or be produced via recombinant DNA techniques well known in the art; see, for example, the techniques described in Sambrook, loc. cit. and Ausubel, loc. cit. The allelic variations may be naturally occurring allelic variants as well as synthetically produced or genetically engineered variants. The proteins, peptides or protein fragments encoded by the various derivatives, allelic variants, homologs or analogs of the above-described nucleic acid molecules may share specific common characteristics, such as molecular weight, immunological reactivity, conformation, etc., as well as physical properties, such as electrophoretic mobility, chromatographic behavior, sedimentation coefficients, pH optimum, temperature optimum, stability, solubility, spectroscopic properties, etc. Preferably, the nucleic acid molecule of the invention contains two ORFs and most preferably, it contains three ORFs. Additionally, nucleic acid molecules representing a genome of a virus and containing four or more ORFs are also preferred embodiments and within the scope of the present invention. Advantageously, the nucleic acid molecules of the present invention do not hybridize to the complementary strand of the genome of TT virus, at least in the region comprised in SEQ ID NO: 26 (comprising the regions encoding for a viral ORF1 , ORF3 and ORF2 with the exception of the about 15 5'terminal nucleotides of ORF2) in the region comprised in SEQ ID NO: 94, SEQ ID NO: 96, SEQ ID NO: 125, SEQ ID NO: 186, SEQ ID NO: 191 and SEQ ID NO: 199 (comprising the regions encoding further viral ORFsl , ORFs2 and ORFs3) or in the region comprised in SEQ ID NO: 95 (comprising yet another ORF1 , ORF2 and ORF3 as well as an ORF4). The genome of TT virus comprises, e.g., genes as deposited in GENEBANK under accession numbers AB011 482, AB01 1486, AB011 487, AB011 488, AB011 489, AB011 490, AB011 491 , AB008 394, AB011 493, AB011 494, AF 055897, AF 06045, AF060546, AF 060 547, AF060 548, AF060 549, AF060 550. Nucleic acid molecules which do not hybridize to the complementary strand of the genome of TT virus can be deduced by the person skilled in the art without further ado, for example by employing hybridization strategies as described in Britten and Davidson in "Nucleic acid hybridisation", edited by Hames and Higgins (1985), IRL Press Oxford. Furthermore, the present invention relates to nucleic acid molecules representing the genome of a virus and having a nucleotide sequence at least 50%, preferably at least 60%, more preferably at least 70%, even more preferably 80% and particularly preferred 95% identical to the DNA sequences as defined in SEQ ID NO: 26, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 125, SEQ ID NO: 186, SEQ ID NO: 191 and SEQ ID NO: 199 above, to nucleic acid molecules having a nucleotide sequence which is at least 60%, preferably 70%, more preferably 80% and particularly preferred 95% identical with the DNA sequences as defined in SEQ ID NO: 24, SEQ ID NO: 34, SEQ ID NO: 75, SEQ ID NO: 87, SEQ ID NO: 118, SEQ ID NO: 179, SEQ ID NO: 187 or SEQ ID NO: 195, supra, or to nucleic acid molecules which contain an ORF or a fragment thereof which is at least 50%, preferably at least 60%, more preferably at least 75% and most preferably at least 90% identical with SEQ ID NO: 31 , SEQ ID NO: 38, SEQ ID NO: 76, SEQ ID NO: 88, SEQ ID NO: 119, SEQ ID NO: 183, SEQ ID NO: 192 or SEQ ID NO: 200, which is at least 50%, preferably at least 60% and more preferably at least 75% identical with the nucleic acid molecule of SEQ ID NO: 28, SEQ ID NO: 39, SEQ ID NO: 89, SEQ ID NO: 184 or SEQ ID NO: 193, at least 60%, preferably at least 70% and more preferably at least 75% identical with SEQ ID NO: 77, SEQ ID NO: 120, SEQ ID NO: 177 or SEQ ID NO: 201 , which is at least 50%, preferably at least 60% and more preferably at least 75% identical with the nucleic acid molecule of SEQ ID NO: 30, SEQ ID NO: 40, SEQ ID NO: 78, SEQ ID NO: 90, SEQ ID NO: 121 , SEQ ID NO: 185, SEQ ID NO: 194 or SEQ ID NO: 202 or which is at least 50%, preferably at least 60% and more preferably at least 75% identical with the nucleic acid molecule of SEQ ID NO: 79; see feature (e), supra. The present invention also relates to nucleic acid molecules representing the genome of a virus and comprising a nucleic acid molecule encoding an amino acid sequence which is at least 35%, preferably at least 40%, more preferably at least 50% and most preferably at least 75% identical with SEQ ID NO: 21 , SEQ ID NO: 25, SEQ ID NO: 27, SEQ ID NO: 29, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61 , SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 80, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 91 , SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 180, SEQ ID NO: 182, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198; see feature (e), above. Furthermore, this invention relates to nucleic acid molecules representing the genome of a virus and encoding an amino acid sequence which is at least 40%, preferably at least 45%, more preferably at least 50% and most preferably at least 75% identical with SEQ ID NO: 81 , SEQ ID NO: 121 , SEQ ID NO: 181 or SEQ ID NO: 188; see feature (e), above. Additionally, the present invention relates to nucleic acid molecules representing the genome of a virus wherein parts of said genome can be amplified under suitable conditions by PCR employing as primers oligonucleotides as defined in SEQ ID NO: 41 and SEQ ID NO: 42 and/or as defined in SEQ ID NO: 115 and SEQ ID NO: 71 , or as defined in SEQ ID NO: 11 , SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 32, SEQ ID NO: 73, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101 , SEQ ID NO: 102, SEQ ID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128; SEQ ID NO: 129, SEQ ID NO: 130, SEQ ID NO: 131 , SEQ ID NO: 132, SEQ ID NO: 135, SEQ ID NO: 136, SEQ ID NO: 172, SEQ ID NO: 173, SEQ ID NO: 174, SEQ ID NO: 175, SEQ ID NO: 176 or SEQ ID NO: 203, SEQ ID NO: 204 or SEQ ID NO: 205 or the complementary strand of such an oligonucleotide. Suitable conditions for the hybridization of said primers to said genome are known to the person skilled in the art and comprise, preferably, stringent conditions. As described herein below, said conditions are described in standard textbooks, such as Sambrook et al., loc. cit. Furthermore, suitable conditions are described in the appended examples, inter alia in Example 10. Using standard technologies, including computer software (like BLAST 2.0) and available databases such as GenBank, the person skilled in the art is, without undue burden, in the position to devise further primers/probes that specifically recognize and/or detect nucleic acid sequences of the invention. These probes/primers are also comprised within the scope of the present invention. Examples of such primers/probes are primers/probes that overlap with the above primers/probes specified by their SEQ ID. The present invention relates furthermore to nucleic acid molecules representing the complementary strand of the above referenced genome and/or ORF(s) or to nucleic acid molecules representing an anti-sense molecule to the above referenced genome and/or ORF(s). Surprisingly, nucleic acid molecules of a new viral agent, distantly related to TT virus have been found. These nucleic acid molecules are detectable only in a minimal fraction of healthy blood donors but have a high dissemination in the blood of intravenous drug users, a population group with a rather high prevalence of parenterally transmittable diseases like chronic liver diseases of unknown etiology (Overby, Curr. Hepatol. 7 (1987), 35). The first identification of these nucleic acid molecules was carried out in a blood sample from an intravenous drug user that has been given the code SEN. For this reason, the new viral agent has the denomination "SEN-virus". As shown herein, SEN-virus or its subtype(s) appear to be selectively segregated in the sera of patients suffering from Non A-Non E hepatitis (NANE hepatitis), in the sera of about 70% of intravenous drug users but could not be detected in sera obtained from healthy blood donors or patients suffering from an autoimmune disease (rheumatoid anthritis and primary biliary cirrhosis) or from hepatitis B (see appended Examples 6, 14 and furthermore, Examples 17 and 19). The fact that some hepatitis delta patients are positive for SENV is not surprising, since most of the patients screened who are positive for both viral agents are intravenous drug users. However, some HBV patients have been screened as also SENV-positive (see appended example 31). These were only a few hepatitis B patients and they were selected not to have a high risk behavior. Further testing of larger cohorts of hepatitis B patients revealed that some of these patients can be co-infected with certain SENV subtypes. While SEN-virus or its subtypes have a low prevalence among healthy blood donors, the majority of patients suffering from advanced liver disease of unknown origin appear to be positive for this (these) viral agent(s). It is assumed in accordance with the invention that SEN-virus comprises different types and subtypes and that some of these subtypes are more pathogenic than others. Furthermore, other pathogenic manifestations than hepatopathies may be caused by this viral agent and/or its subtypes. Such pathogenic manifestations comprise, but are by no means limited to disorders of the gastrointestinal tract and/or proliferative disorders. These disorders comprise Crohn's disease (or other inflammatory bowel diseases), lupus erythematosus, as well as cancers, like hepatocarcinomas and coloncarcinomas (see appended examples 17, 19 and 26). In addition, other pathogenic agents or genetic or other dispositions may be involved in the onset of said hepatopathies. All the above referenced types and subtypes are comprised by the present invention. The present invention furthermore relates to a nucleic acid representing the genome of said virus which deviates by insertion, substitution, deletion, inversion or duplication from the genome specified above and comprises at least one ORF, preferably two ORFs and most preferably the three different ORFs specified above. Additionally, this invention comprises a nucleic acid representing the genome of said virus which deviates by insertion, substitution, deletion, inversion or duplication from the genome specified above that comprises at least four ORFs as specified herein- above. Furthermore, the present invention relates to a nucleic acid molecule encoding a viral (poly)peptide or a fragment thereof, wherein said nucleic acid molecule (a) contains at least one ORF which encodes a polypeptide having the amino acid sequence of SEQ ID NO: 21 , SEQ ID NO: 25, SEQ ID NO: 27, SEQ ID NO: 29, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 80, SEQ ID NO: 81 , SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 91 , SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO. 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 180, SEQ ID NO: 181 , SEQ ID NO: 182, SEQ ID NO: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 196, SEQ ID NO: 197 or SEQ ID NO: 198 or a fragment thereof of at least 6 amino acids; (b) has the sequence identified in SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 20, SEQ ID NO: 26, SEQ ID NO: 28 , SEQ ID NO: 30, SEQ ID NO: 31 , SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51 , SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121 , SEQ ID NO: 125, SEQ ID NO: 177, SEQ ID NO: 179, SEQ ID NO: 183, SEQ ID NO: 184, SEQ ID NO: 185, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 191 , SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201 or SEQ ID NO: 202 or a fragment thereof of at least 12 nucleotides; (c) has the sequence identified in SEQ ID NO: 24, SEQ ID NO: 34, SEQ ID NO: 75, SEQ ID NO: 87, SEQ ID NO: 118, SEQ ID NO: 179, SEQ ID NO: 187 or SEQ ID NO: 195; (d) hybridizes under stringent conditions to the complementary strand of the nucleic acid molecule of SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 20, SEQ ID NO: 28 ,SEQ ID NO: 30, SEQ ID NO: 31 , SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51 , SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121 , SEQ ID NO: 125, SEQ ID NO: 177, SEQ ID NO: 179, SEQ ID NO: 183, SEQ ID NO: 184, SEQ ID NO: 185, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 191 , SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201 or SEQ ID NO: 202; (e) is degenerate with respect to the nucleic acid molecule of (d) but does not hybridize to the complementary strand of the genome of TT virus encoding TTV ORF1 and/or TTV ORF2; (f) encodes a polypeptide which is at least 35%, preferably at least 40%, more preferably at least 50% and most preferably at least 75% identical with SEQ ID NO: 21 , SEQ ID NO: 25, SEQ ID NO: 27, SEQ ID NO: 29, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 80, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 91 , SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 123, SEQ ID NO: 124 or SEQ ID NO: 180, SEQ ID NO: 182, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198 or encodes a polypeptide which is at least 40%, preferably at least 50%, more preferably at least 60% and most preferably at least 75% identical with SEQ ID NO: 81 , SEQ ID NO: 122, SEQ ID NO: 181 or SEQ ID NO: 188; or (g) is at least 50%, preferably at least 60%, more preferably at least 75% and most preferably at least 90% identical with the sequence specified in (b) or at least 60%, preferably at least 70%, more preferably at least 80% and most preferably at least 90% identical with the sequence specified in (c); or (h) it deviates from any of the above molecules by insertion, substitution, deletion, inversion, duplication, recombination, addition or a combination thereof; or (i) parts of it can be amplified under suitable conditions by PCR employing as primers oligonucleotides as defined in SEQ ID NO: 41 and SEQ ID NO: 42 and/or as defined in SEQ ID NO: 1 15 and SEQ ID NO: 71 or as defined in SEQ ID NO: 11 , SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 32, SEQ ID NO: 73, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101 , SEQ ID NO: 102, SEQ ID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128; SEQ ID NO: 129, SEQ ID NO: 130, SEQ ID NO: 131 , SEQ ID NO: 132, SEQ ID NO: 135, SEQ ID NO: 136, SEQ ID NO: 172, SEQ ID NO: 173, SEQ ID NO: 174, SEQ ID NO: 175, SEQ ID NO: 176 or SEQ ID NO: 203, SEQ ID NO: 204 or SEQ ID NO: 205 or the complementary strand of such an oligonucleotide. Preferably, said nucleic acid molecule contains two ORFs and most preferably, it contains three ORFs. Additionally and also preferably, said nucleid acid molecules may comprise four or more ORFs. Additionally, it is preferred that said fragment in feature (a) comprises at least 8 amino acids, more preferably at least 10 amino acids, more preferably at least 12 amino acids, more preferably at least 15 amino acids, more preferably at least 20 amino acids, even more preferably at least 30 amino acid, and most preferably at least 35 amino acids. Also preferably, said fragment in feature (b) comprises at least 15, more preferably at least 18 nucleotides, even more preferably at least 21 nucleotides, and most preferably at least 28 nucleotides. The invention also relates to a nucleic acid molecule encoding the above viral polypeptide or a fragment thereof wherein said polypeptide deviates by one or more amino acid substitutions, amino acid deletions, amino acid insertions, amino acid inversions, amino acid additions, amino acid recombinations or amino acid duplications or a combination thereof from the above-identified sequence. Additionally, the present invention provides for a nucleic acid molecule specifically hybridizing to the complementary strand of the nucleic acid molecule having the nucleic acid sequence of SEQ ID NO: 26, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 125, SEQ ID NO: 186, SEQ ID NO: 191 or SEQ ID NO: 199 specified above or to said nucleic acid molecule or being identical to said nucleic acid molecule or to said complementary strand thereof wherein said nucleic acid molecule comprises at least 12 nucleotides, preferably at least 15, more preferably at least 18 nucleotides, more preferably at least 21 nucleotides and most preferably at least 25 nucleotides. Said nucleic acid molecule comprises coding, non-coding sequences, sequences which are complementary to the coding strand and, whenever applicable, antisense sequences. Examples for viral-non coding sequences are 5' and 3' terminal sequences, like 3'UTRs or 5' IRES (internal ribosome entry site), or 5' and 3' repetitive sequences. They may comprise regulatory sequences for the initiation of transcription. Furthermore, such non-coding regions can be intron sequences. The nucleic acid molecule may also extend 5' or 3' to the above specified SEQ ID NO: 26, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 125, SEQ ID NO: 186, SEQ ID NO: 191 or SEQ ID NO: 199 either when having the identical nucleotide sequence in the overlapping parts of said sequence or the complementary sequence, when hybridizing thereto or when hybridizing to its complementary strand. In a preferred embodiment, said fragment of the nucleic acid molecule of the present invention encodes an epitope that reacts with antibodies specific for SEN virus. This means that these epitopes do not react with antibodies specific for hepatitis, A, B, C, D, E, G, Non B-E or TT virus. In yet another preferred embodiment, the nucleic acid molecule of the present invention is a probe or primer. Said probe or primer can comprise the sequence(s) as defined in SEQ ID NO: 11 , SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 32, SEQ ID NO: 41 , SEQ ID NO: 42, SEQ ID NO: 71 , SEQ ID NO: 73, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101 , SEQ ID NO: 102, SEQ ID NO: 115, SEQ ID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128; SEQ ID NO: 129, SEQ ID NO: 130, SEQ ID NO: 131 , SEQ ID NO: 132, SEQ ID NO: 135, SEQ ID NO: 136, SEQ ID NO: 172, SEQ ID NO: 173, SEQ ID NO: 174, SEQ ID NO: 175, SEQ ID NO: 176 or SEQ ID NO: 203, SEQ ID NO: 204 or SEQ ID NO: 205. It is understood within the scope of this invention that the specific primers may also be employed as (specific) probes. These primers can be used in a PCR reaction for amplifying the intervening sequence or, alternatively can be used as probes for directly detecting the virus/viral nucleic acid without amplification. SEQ ID NO: 13 can also be used for detecting the PCR product obtained with SEQ ID NO: 11 and SEQ ID NO: 12 and/or with SEQ ID NO: 126 and SEQ ID NO: 127. Similarly, SEQ ID NO: 98 can be used for detecting the PCR product obtained with SEQ ID NOs: 115 and 71 , SEQ ID NO: 130 can be employed to detect the PCR product obtained with SEQ ID NOs: 128 and 71 , SEQ ID NO: 173 might be employed to detect the PCR product obtained with SEQ ID NOs: 172 and 71 , SEQ ID NO: 176 can be used to verify the PCR product obtained with SEQ ID NOs: 174 and 175 and SEQ ID NO: 205 can be used to detect the PCR product obtained with SEQ ID NOs: 203 and 204. Alternatively, a primer having SEQ ID NO: 13 or primers having SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 32, SEQ ID NO: 41 , SEQ ID NO: 42, SEQ ID NO: 71 , SEQ ID NO: 73, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101 , SEQ ID NO: 102, SEQ ID NO: 115, SEQ ID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, SEQ ID NO: 131 , SEQ ID NO: 132, SEQ ID NO: 135, SEQ ID NO: 136, SEQ ID NO: 172, SEQ ID NO: 173, SEQ ID NO: 174, SEQ ID NO: 175, SEQ ID NO: 176, SEQ ID NO: 203, SEQ ID NO: 204 or SEQ ID NO: 205 can be used for directly detecting the viral DNA, and therefore the virus, without amplification. Furthermore, said primers or their complements can be used in PCR reactions or similar methods in combination with primers derived from known viral sequences such as, inter alia, primers as shown in SEQ ID NO:1 , SEQ ID NO: 33, SEQ ID NO: 72, SEQ ID NO: 74, SEQ ID NO: 86 or SEQ ID NO: 178. The nucleic acid molecule of the invention may be DNA such as cDNA or RNA such as mRNA. Additionally, the nucleic acid molecule of the invention may be PNA (peptide nucleic acid). Its origin may be natural, synthetic or semisynthetic or it may be a derivative. Furthermore, said nucleic acid molecule may be a recombinantly produced chimeric nucleic acid molecule comprising any of the aforementioned nucleic acid molecules either alone or in combination. Preferably, said nucleic acid molecule is part of a vector. The present invention therefore also relates to a vector comprising the nucleic acid molecule of the present invention. The vector of the present invention may be, e.g., a plasmid, cosmid, virus, bacteriophage or another vector used e.g. conventionally in genetic engineering, and may comprise further genes such as marker genes which allow for the selection of said vector in a suitable host cell and under suitable conditions. Furthermore, the vector of the present invention may, in addition to the nucleic acid sequences of the invention, comprise expression control elements, allowing proper expression of the coding regions in suitable hosts. Such control elements are known to the artisan and may include a promoter, translation initiation codon, and translation sites. This vector may also include insertion sites for introducing an insert into the vector. Preferably, the nucleic acid molecule of the invention is operatively linked to said expression control sequences allowing expression in eukaryotic or prokaryotic cells. Control elements ensuring expression in eukaryotic and prokaryotic cells are well known to those skilled in the art. As mentioned above, they usually comprise regulatory sequences ensuring initiation of transcription and optionally poly-A signals ensuring termination of transcription and stabilization of the transcript. Additional regulatory elements may include transcriptional as well as translational enhancers, and/or naturally-associated or heterologous promoter regions. Possible regulatory elements permitting expression in for example mammalian host cells comprise the CMV- HSV thymikine kinase promoter, SV40, RSV-promoter (Rous sarcome virus), human elongation factor 1 α-promoter, CMV enhancer or SV40-enhancer. For the expression in prokaryotic cells, a multitude of promoters including, for example, the tac-lac-promoter or the trp promoter, has been described. Besides elements which are responsible for the initiation of transcription such regulatory elements may also comprise transcription termination signals, such as SV40-poly-A site or the tk-poly-A site, downstream of the polynucleotide. In this context, suitable expression vectors are known in the art such as Okayama-Berg cDNA expression vector pcDV1 (Pharmacia), pRc/CMV, pcDNAI , pcDNA3 (In-vitrogene), pSPORTI (GIBCO BRL), or prokaryotic expression vectors, such as lambda gt11. Beside the nucleic acid molecules of the present invention, the vector may further comprise nucleic acid sequences encoding for secretion signals. Such sequences are well known to the person skilled in the art. Furthermore, depending on the expression system used leader sequences capable of directing the polypeptide to a cellular compartment may be added to the coding sequence of the nucleic acid molecules of the invention and are well known in the art. The leader sequence(s) is (are) assembled in appropriate phase with translation, initiation and termination sequences, and preferably, a leader sequence capable of directing secretion of translated protein, or a portion thereof, into the periplasmic space or extracellular medium. Optionally, the heterologous sequence can encode a fusion protein including an C- or N-terminal identification peptide imparting desired characteristics, e.g., stabilization or simplified purification of expressed recombinant product. Once the vector has been incorporated into the appropriate host, the host is maintained under conditions suitable for high level expression of the nucleotide sequences, and, as desired, the collection and purification of the (poly)peptide(s) or fragments thereof of the invention may follow. Of course, the vector can also comprise regulatory regions from the viral agent of the invention. Furthermore, the vector of the present invention may also be a gene transfer or targeting vector. Gene therapy, which is based on introducing therapeutic genes, for example for vaccination into cells by ex-vivo or in-vivo techniques is one of the most important applications of gene transfer. Suitable vectors, methods or gene-delivering systems for in-vitro or in-vivo gene therapy are described in the literature and are known to the person skilled in the art; see, e.g., Giordano, Nature Medicine 2 (1996), 534-539; Schaper, Circ. Res. 79 (1996), 911-919; Anderson, Science 256 (1992), 808-813, Isner, Lancet 348 (1996), 370-374; Muhlhauser, Circ. Res. 77 (1995), 1077- 1086; Onodua, Blood 91 (1998), 30-36; Verzeletti, Hum. Gene Ther. 9 (1998), 2243- 2251 ; Verma, Nature 389 (1997), 239-242; Anderson, Nature 392 (Supp. 1998), 25- 30; Wang, Gene Therapy 4 (1997), 393-400; Wang, Nature Medicine 2 (1996), 714- 716; WO 94/29469; WO 97/00957; US 5,580,859; US 5,589,466; US 4,394,448 or Schaper, Current Opinion in Biotechnology 7 (1996), 635-640, and references cited therein. The nucleic acid molecules and vectors of the invention may be designed for direct introduction, e.g. by biolistic methods, or for introduction via liposomes, or viral vectors (e.g. adenoviral, retroviral) into the cell. Additionally, a baculoviral system can be used as eukaryotic expression system for the nucleic acid molecules of the invention. The present invention also relates to a host cell transfected or transformed with the vector of the invention or a non-human host carrying the vector of the present invention, i.e. to a host cell or host which is genetically modified with a nucleic acid molecule according to the invention or with a vector comprising such a nucleic acid molecule. The term "genetically modified" means that the host cell or host comprises in addition to its natural genome a nucleic acid molecule or vector according to the invention which was introduced into the cell or host or into one of its predecessors/parents. The nucleic acid molecule or vector may be present in the genetically modified host cell or host either as an independent molecule outside the genome, preferably as a molecule which is capable of replication, or it may be stably integrated into the genome of the host cell or host. The host cell of the present invention may be any prokaryotic or eukaryotic cell. Suitable prokaryotic cells are those generally used for cloning like E. coli or Bacillus subtilis. Furthermore, eukaryotic cells comprise, for example, fungal or animal cells. Examples for suitable fungal cells are yeast cells, preferably those of the genus Saccharomyces and most preferably those of the species Saccharomyces cerevisiae. Suitable animal cells are, for instance, insect cells, vertebrate cells, preferably mammalian cells, and most preferably non-neuronal cells, such as e.g. CHO, Hela, NIH3T3, MOLT-4, Jurkat, K562, HepG2. Further suitable cell lines known in the art are obtainable from cell line depositories, like the American Type Culture Collection (ATCC). Moreover, in yet another preferred embodiment, the invention relates to a host cell which is in vitro infected or transfected with the virus/viral agent of the present invention. In a more preferred embodiment the host cell which is in vitro infected or transfected with the virus of the invention is a hepatic cell, a macrophage, a lymphocyte, an epithelial cell or an osteocyte or a cell (line) derived therefrom. Host may be mammals, most preferably monkey or apes. Said mammals may be indispensable for developing a cure, preferably a vaccine against the viral agent. Furthermore, the present invention relates to a method of producing a (poly)peptide encoded by the nucleic acid molecule of the invention comprising culturing the host cell of the present invention under suitable conditions that allow the synthesis of said (poly)peptide and recovering and/or isolating the (poly)peptide produced from the culture. The transformed hosts can be grown in fermentors and cultured according to techniques known in the art to achieve optimal cell growth. The (poly)peptide of the invention can then be isolated from the growth medium, cellular lysates, or cellular membrane fractions. Once expressed, the protein of the present invention can be purified according to standard procedures of the art, including ammonium sulfate precipitation, affinity columns, column chromatography, gel electrophoressis and the like; see, Scopes, "Protein Purification", Springer- Verlag, N.Y. (1982). Substantially pure proteins of at least about 90 to 95% homogeneity are preferred, and 98 to 99% or more homogeneity are most preferred, for pharmaceutical uses. Once purified, partially or to homogeneity as desired, the proteins may then be used therapeutically (including extracorporeally) or in developing and performing assay procedures. Additionally, the present invention relates to a (poly)peptide encoded by the nucleic acid molecule of the invention or produced by or obtainable by the above-described method. The term "(poly)peptide" denotes either a peptide or a polypeptide. The (poly)peptides of the present invention may be recombinant (poly)peptides expressed in host cells like bacteria, yeasts, or other eukaryotic cells, like mammalian or insect cells. Alternatively, they may be isolated from viral preparations. In another embodiment of the present invention, synthetic (poly)peptides may be used. Therefore, such a (poly)peptide may be a (poly)peptide as encoded by the nucleic acid molecule of the invention which only comprises naturally occurring amino acid residues, but it may also be a (poly)peptide containing modifications. These include covalent derivatives, such as aliphatic esters or amides of a carboxyl group, O-acetyl derivatives of hydroxyl containing residues and N-acyl derivatives of amino group containing residues. Such derivatives can be prepared by linkage to reactable groups which are present in the side chains of amino acid residues and at the N- and C-terminus of the protein. Furthermore, the (poly)peptide can be radiolabeled or labeled with a detectable group, such as a covalently bound rare earth chelate, or conjugated to a fluorescent moiety. The (poly)peptide of the present invention can be, for example, the product of expression of a nucleotide sequence encoding such a (poly)peptide, a product of chemical modification or can be purified from natural sources, for example, viral preparations. Furthermore, it can be the product of covalent linkage of (poly)peptide domains. In addition, amino acid sequences representing the (poly)peptide(s) of the present invention can be easily chemically synthesized using synthesizers which are well known in the art and are commercially available. Moreover, the present invention relates to a virus or viral agent carrying the genome represented by the nucleic acid molecule of the present invention. In a more preferred embodiment, the present invention relates to a virus or viral agent which has a genomic sequence which comprises at least 3 ORFs, wherein parts of said genomic sequence can be amplified under suitable conditions by PCR employing as primers oligonucleotides as defined in SEQ ID NO: 41 and SEQ ID NO: 42, as defined in SEQ ID NO: 115 and SEQ ID NO: 71 , as defined in SEQ ID NO: 126 and SEQ ID NO: 127, as defined in SEQ ID NO: 128 and SEQ ID NO: 71 , as defined in SEQ ID NO: 172 and SEQ ID NO: 71 , as defined in SEQ ID NO: 174 and SEQ ID NO: 175 or as defined in SEQ ID NO: 203 and SEQ ID NO: 204 or as defined in any one of SEQ ID NO: 1 1 , SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO 18, SEQ ID NO: 19, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 32, SEQ ID NO 73, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO 99, SEQ ID NO: 100, SEQ ID NO: 101 , SEQ ID NO: 102, SEQ ID NO: 129, SEQ ID NO: 130, SEQ ID NO: 131 , SEQ ID NO: 132, SEQ ID NO: 135, SEQ ID NO: 136, SEQ ID NO: 173, SEQ ID NO: 176 or SEQ ID NO: 205, or an oligonucleotide having a complementary sequence. Suitable conditions under which genomic sequences can be amplified are well known to the person skilled in the art, as shown, inter alia, in Sambrook , Molecular Cloning A Laboratory Manual, Cold Spring Harbor Laboratory (1989) N.Y., or as demonstrated in the appended examples. in a yet more preferred embodiment, this virus or viral agent is a SEN virus. SEN virus means a virus, virus type, virus class, virus genotype or virus subtype, e.g., SENV-A, SENV-B, SENV-C, SENV-D, SENV-E, SENV-F, SENV-G or SENV-H which comprises a genome having at least one ORF, preferably two, most preferably the three and/or particularly preferred the four different ORFs identified above. Furthermore, the SEN virus/viral agent of the present invention can be a derivative, such as non-pathogenic derivative, of the virus/viral agent specified above, preferably an attenuated virus. An attenuated virus/viral agent is a selected strain of a virulent virus which does not cause the clinical signs associated with the parent virus but still replicates well enough to induce immunity. The person skilled in the art knows of the methods commonly used to obtain such attenuated viral strains. Methods may follow conventional protocols as described, for example in Mahy, BWJ and Kangro, H. O., "Virology Method Manual", Academic Press London (1996). Attenuation may be achieved by heat or chemical treatment or by genetic engineering in which the virus is deprived of its pathogenic genes or parts of them. Attenuated strains are usually obtained by passage in cell culture or in a host different from the natural host. Alternatively, an attenuated strain may be constructed utilizing the genomic information of SEN virus provided herein, and employing recombinant techniques. These attenuated strains are useful for vaccines or for the isolation of antigens. Additionally, the SEN virus of the present invention can be a chimeric virus comprising at least one ORF, preferably two ORFs, more preferably three ORFs and most preferably four different ORFs of this invention in combination with one or more ORFs from other viral agents, such as, inter alia, TT virus and/or ORF(s) from viruses specific for hepatitis A, B, D, E, G, Non-A-Non-E or any other virus suitable for genetic manipulation. The person skilled in the art is enabled by modern, molecular biological methods, such as in vivo and in vitro recombination, to generate pathogenic and non-pathogenic viral chimeras consisting of elements from different, even non-related viruses. One objective is that such resulting chimeras such as, inter alia, immunogenic virus-like particles (VLPs), can be used in medical treatment and prevention as well as in basic medical and biological research. Systems for the production of VLPs are known to the person skilled in the art and are described, e.g. in Ulrich, Intervirology 39 (1996), 126-132. Furthermore, the present invention relates to a method for producing the virus or viral agent of the invention comprising culturing the above-mentioned host cell under suitable conditions and isolating the virus from the culture. For this purpose, supernatants from said cultures can be harvested or infected cells can be lysed in order to obtain the produced virus. Common methods are, for example, described in Harden MR, "Approaches to anti-viral agents", VCH Pub. (Eds.), (1986). In the most preferred embodiment, the virus of the present invention, the virus or viral agent produced by the method described above is transmissible by blood. Furthermore, the invention relates to a (poly)peptide isolated from viral preparations, wherein said viral preparation comprises a virus of the invention. Inter alia, viral (poly)peptides can be isolated and/or prepared using chromatographic methods, like affinity chromatography employing antibodies directed against these (poly)peptides. The present invention additionally relates to an antibody or a fragment or derivative thereof or an antiserum of an aptamer or another receptor specifically recognizing an epitope on the nucleic acid, the (poly)peptide or on the virus or viral agent of the invention. The general methodology for producing antibodies is well-known and has, for monoclonal antibodies, been described in, for example, Kδhler and Milstein, Nature 256 (1975), 494 and reviewed in J.G.R. Hurrel, ed., "Monoclonal Hybridoma Antibodies: Techniques and Applications", CRC Press Inc., Boco Raron, FL (1982), as well as that taught by L. T. Mimms et al., Virology 176 (1990), 604-619. In accordance with the present invention the term "antibody" relates to monoclonal or polyclonal antibodies. Polyclonal antibodies (antiserum) can be obtained according to conventional protocols. Antibody fragments or derivatives comprise F(ab') 2 , Fab, Fv or scFv fragments; see, for example, Harlow and Lane, "Antibodies, A Laboratory Manual", CSH Press 1988, Cold Spring Harbor, NY. Preferably the antibody of the invention is a monoclonal antibody. Furthermore, in accordance with the present invention, the derivatives of the invention can be produced by peptidomimetics. In the context of the present invention, the term "aptamer" comprises nucleic acids such as RNA, ssDNA (ss = single stranded), modified RNA, modified ssDNA or PNAs which bind a plurality of target sequences having a high specificity and affinity. Said other receptors may, for example, be derived from said antibody etc. by peptidomimetics. The specificity of the recognition implies that other known viruses such as TTV are not bound. A suitable test for assessing the specificity would imply contacting the above recited compound comprising the epitope of the invention as well as corresponding compounds e.g. from TTV, for example in an ELISA format and identifying those antibodies etc. that only bind to the compound of the invention but do not or to no significant extent cross-react with said corresponding compounds. The invention further relates to a derivative of the (poly)peptide of the invention which is specifically recognized by the antibody or fragment or derivative thereof or an aptamer of the invention. Such derivatives can be (semi)synthetically, e.g. chemically produced. Production methods may also employ peptidomimetics. Such production methods are well known in the art and can be applied by the person skilled in the art without further ado. Furthermore, the present invention relates to a hybridoma producing the antibody of the present invention. The preparation of a hybridoma is well known to the artisan, see, for example, Harlow and Lane, loc. cit. The present invention also relates to a fusion protein comprising the (poly)peptide of the present invention. In addition to the (poly)peptides of the present invention said fusion protein can comprise at least one further domain, said domain being linked by covalent or non-covalent bonds. The linkage can be based on a genetic fusion according to the methods known in the art (Sambrook et al., loc. cit., Ausubel, "Current Protocols in Molecular Biology", Green Publishing Associates and Wiley Interscience, N.Y. (1989)) or can be performed by, e.g., chemical cross-linking as described in, e.g., WO 94/04686. The additional domain present in the fusion protein comprising the (poly)peptide of the invention may preferably be linked by a flexible linker, advantageously a polypeptide linker, wherein said polypeptide linker comprises plural, hydrophiiic, peptide-bonded amino acids of a length sufficient to span the distance between the C-terminal end of said further domain and the N- terminal end of the peptide, polypeptide or antibody or vice versa. The above described fusion protein may further comprise a cleavable linker or cleavage site, which, for example, is specifically recognized and cleaved by proteinases or chemical agents. Additionally, said at least one further domain may be of a predefined specificity or function. In this context, it is understood that the (poly)peptides of the invention may be further modified by conventional methods known in the art. This allows for the construction of fusion proteins comprising the (poly)peptide of the invention and other functional amino acid sequences, e.g., nuclear localization signals, transactivating domains, DNA-binding domains, hormone-binding domains, protein tags (e.g. GST, GFP, h-myc peptide, FLAG, HA peptide) which may be derived from heterologous proteins. In yet another embodiment, the present invention relates to a mosaic polypeptide comprising at least two epitopes of the (poly)peptide of the invention or the virus of the invention wherein said mosaic polypeptide lacks amino acids normally intervening between the epitopes in the native SEN virus genome. Inter alia, such mosaic polypeptides are useful in the applications and methods described herein, since they may comprise within a single peptide or (poly)peptide a number of immunologically relevant epitopes possibly presented linearly or as multi- antigen peptide system in a case of lysines. Relevant epitopes can be separated by spacer regions. In another embodiment, the present invention relates to the nucleic acid molecule, the (poly)peptide, the derivative of the (poly)peptide, the virus, the antibody or fragment or derivative thereof, the aptamer or other receptor, the fusion protein, the mosaic polypeptide, or the primer of the invention which is detectably labeled. A variety of techniques are available for labeling biomolecules, are well known to the person skilled in the art and are considered to be within the scope of the present invention. Such techniques are, e.g., described in Tijssen, "Practice and theory of enzyme immuno assays", Burden, RH and von Knippenburg (Eds), Volume 15 (1985), "Basic methods in molecular biology"; Davis LG, Dibmer MD; Battey Elsevier (1990), Mayer et al., (Eds) "Immunochemical methods in cell and molecular biology" Academic Press, London (1987), or in the series "Methods in Enzymology", Academic Press, Inc. There are many different labels and methods of labeling known to those of ordinary skill in the art. Examples of the types of labels which can be used in the present invention include enzymes, radioisotopes, colloidal metals, fluorescent compounds, chemiluminescent compounds, and bioluminescent compounds. Commonly used labels comprise, inter alia, fluorochromes (like fluorescein, rhodamine, Texas Red, etc.), enzymes (like horse radish peroxidase, β- galactosidase, alkaline phosphatase), radioactive isotopes (like 32 P or 125 l), biotin, digoxygenin, colloidal metals, chemi- or bioluminescent compounds (like dioxetanes, luminol or acridiniums). Labeling procedures, like covalent coupling of enzymes or biotinyl groups, iodinations, phosphorylations, biotinylations, random priming, nick- translations, tailing (using terminal transferases) are well known in the art. Detection methods comprise, but are not limited to, autoradiography, fluorescence microscopy, direct and indirect enzymatic reactions, etc. In addition, the present invention relates to a solid phase which is attached to (a) the nucleic acid molecule; (b) the (poly)peptide; (c) the derivative of said (poly)peptide; (d) the virus/viral agent; (e) the antibody or fragment or derivative thereof or the aptamer or other receptor; (f) the fusion protein; and/or (g) the mosaic polypeptide, all as described above. Solid phases are known to those in the art and may comprise polystyrene beads, latex beads, magnetic beads, colloid metal particles, glass and/or silicon chips and surfaces, nitrocellulose strips, membranes, sheets, animal red blood cells, or red blood cell ghosts, duracytes and the walls of wells of a reaction tray, plastic tubes or other test tubes. Suitable methods of immobilizing nucleic acids, (poly)peptides, proteins, antibodies, viruses, etc. on solid phases include but are not limited to ionic, hydrophobic, covalent interactions and the like. The solid phase can retain one or more additional receptor(s) which has/have the ability to attract and immobilize the region as defined above. This receptor can comprise a charged substance that is oppositely charged with respect to the reagent itself or to a charged substance conjugated to the capture reagent or the receptor can be any specific binding partner which is immobilized upon (attached to) the solid phase and which is able to immobilize the reagent as defined above. Commonly used detection assays comprise radioisotopic or non-radioisotopic methods. These comprise, inter alia, R1A (Radioimmuno Assay) and IRMA (Immune Radioimmunometric Assay), EIA (Enzym Immuno Assay), ELISA (Enzyme Linked Immuno Sorbent Assay), FIA (Fluorescent Immuno Assay), and CLIA (Chemioluminescent Immune Assay). Other detection methods that are used in the art are those that do not utilize tracer molecules. One prototype of these methods is the agglutination assay, based on the property of a given molecule to bridge at least two particles. As is evident to the person skilled in the art, the demand for specific and sensitive methods for screening and identifying carriers of SEN-viruses and contaminated body fluids or blood products is significant. Therefore, in another aspect, the present invention relates to a diagnostic composition comprising (a) the solid phase; (b) the nucleic acid molecule; (c) the (poly)peptide; (d) the derivative of said (poly)peptide; (e) the virus or viral agent; (f) the antibody or fragment or derivative thereof or the aptamer or other receptor; (g) the fusion protein; (h) a primer or a pair of primers; and/or (i) the mosaic polypeptide of the present invention, ail as described above. For diagnosis and quantification of viruses, viral fragments, derivatives, (poly)peptides, polynucleotides, etc. in clinical and/or scientific specimens, a variety of immunological methods, as described above as well as molecular biological methods, like nucleic acid hybridization assays, PCR assays or DNA Enzyme Immunoassays (Mantero et al., Clinical Chemistry 37 (1991), 422-429) have been developed and are well known in the art. In this context, it should be noted that the nucleic acid molecules of the invention may also comprise PNAs, modified DNA analogs containing amide backbone linkages. Such PNAs are useful, inter alia, as probes for DNA/RNA hybridization. The (poly)peptide of the invention may be, inter alia, useful for the detection of anti-viral antibodies in biological test samples of infected individuals. It is also contemplated that antibodies of the invention may be useful in discriminating acute from non-acute infections. The diagnostic composition optionally comprises suitable means for detection. The (poly)peptides and antibodies or fragments or derivatives thereof or aptamers etc. described above are, for example, suitable for use in immunoassays in which they can be utilized in liquid phase or bound to a solid phase carrier. Examples of immunoassays which can utilize said (poly)peptide are competitive and non- competitive immunoassays in either a direct or indirect format. Examples of such immunoassays as already described above, are the radioimmunoassay (RIA), the sandwich (immunometric assay) and the Western blot assay. The (poly)peptides, antibodies, mosaic polypeptides and/or fusion proteins etc. can be bound to many different carriers. Examples of well-known carriers include glass, polystyrene, polyvinyl chloride, polypropylene, polyethylene, polycarbonate, dextran, nylon, amyloses, natural and modified celluloses, polyacrylamides, agaroses, and magnetite. The nature of the carrier can be either soluble or insoluble for the purposes of the invention. Appropriate labels and methods for labeling have been identified above. Said diagnostic compositions may be used in methods for detecting expression of a nucleic acid molecule of the invention by detecting the presence of mRNA coding for a (poly)peptide or viral protein of the invention which comprises, for example, obtaining mRNA from viral preparations and contacting the mRNA so obtained with a probe/primer comprising a nucleic acid molecule capable of specifically hybridizing with a polynucleotide of the invention under suitable conditions (see also supra), and detecting the presence of mRNA hybridized to the probe/primer. Further diagnostic methods leading to the detection of nucleic acid molecules in a sample comprise, e.g., polymerase chain reaction (PCR), ligase chain reaction (LCR), Southern blotting in combination with nucleic acid hybridization, comparative genome hybridization (CGH) or representative difference analysis (RDA). These methods for assaying for the presence of nucleic acid molecules are known in the art and can be carried out without any undue experimentation. Of course, the diagnostic composition can also be employed for the detection of virus, viral (poly)peptide or another nucleic acid molecule of the invention such as the viral genome. The present invention further relates to a kit comprising (a) the solid phase; (b) the nucleic acid molecule; (c) the (poly)peptide; (d) the derivative of the (poly)peptide; (e) the virus or viral agent; (f) the antibody or fragment or derivative thereof or the aptamer or other receptor; (g) the fusion protein; (h) a primer or a pair of primers; and/or (i) the mosaic polypeptide as described above. Advantageously, the kit of the present invention further comprises, optionally (a) reaction buffer(s), storage solutions and/or remaining reagents or materials required for the conduct of scientific or diagnostic assays or the like. Furthermore, parts of the kit of the invention can be packaged individually in vials or bottles or in combination in containers or multicontainer units. The kit of the present invention may be advantageously used, inter alia, for carrying out the method of producing a (poly)peptide of the invention and could be employed in a variety of applications referred herein, e.g., as diagnostic kits, as research tools or vaccination tools. Additionally, the kit of the invention may contain means for detection suitable for scientific medical and/or diagnostic purposes. The manufacture of the kits follows preferably standard procedures which are known to the person skilled in the art. Furthermore, in another embodiment, the present invention relates to a composition comprising (a) the nucleic acid molecule; (b) the (poly)peptide; (c) the derivative of the (poly)peptides; (d) the attenuated virus; (e) the non-pathogenic derivative; (f) the antibody or fragment or derivative thereof or the aptamer or other receptor; (g) the fusion protein; and/or (h) the mosaic polypeptide of the present invention. In a more preferred embodiment said composition is a pharmaceutical composition. The pharmaceutical composition of the present invention may further comprise a pharmaceutically acceptable carrier, excipient and/or diluent. Examples of suitable pharmaceutical carriers are well known in the art and include phosphate buffered saline solutions, water, emulsions, such as oil/water emulsions, various types of wetting agents, sterile solutions etc. Compositions comprising such carriers can be formulated by well known conventional methods. These pharmaceutical compositions can be administered to the subject at a suitable dose. Administration of the suitable compositions may be effected by different ways, e.g., by intravenous, intraperitoneal, subcutaneous, intramuscular, topical, intradermal, intranasal or intrabronchial administration. The dosage regimen will be determined by the attending physician and clinical factors. As is well known in the medical arts, dosages for any one patient depend upon many factors, including the patient's size, body surface area, age, the particular compound to be administered, sex, time and route of administration, general health, and other drugs being administered concurrently. Proteinaceous pharmaceutically active matter may be present in amounts between 1 ng and 10 mg per dose; however, doses below or above this exemplary range are envisioned, especially considering the aforementioned factors. Administration of the suitable compositions may be effected by different ways, e.g., by intravenous, intraperitoneal, subcutaneous, intramuscular, topical or intradermal administration. If the regimen is a continuous infusion, it should also be in the range of 1 μg to 10 mg units per kilogram of body weight per minute, respectively. Progress can be monitored by periodic assessment. The compositions of the invention may be administered locally or systemically. Administration will generally be parenterally, e.g., intravenously. The compositions of the invention may also be administered directly to the target site, e.g., by biolistic delivery to an internal or external target site or by catheter to a site in an artery. Preparations for parenteral administration include sterile aqueous or non-aqueous solutions, suspensions, and emulsions. Examples of non-aqueous solvents are propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable organic esters such as ethyl oleate. Aqueous carriers include water, alcoholic/aqueous solutions, emulsions or suspensions, including saline and buffered media. Parenteral vehicles include sodium chloride solution, Ringer's dextrose, dextrose and sodium chloride, lactated Ringer's, or fixed oils. Intravenous vehicles include fluid and nutrient replenishers, electrolyte replenishers (such as those based on Ringer's dextrose), and the like. Preservatives and other additives may also be present such as, for example, antimicrobials, anti-oxidants, chelating agents, and inert gases and the like. Furthermore, the pharmaceutical composition of the invention may comprise further agents such as interleukins, interferons and/or CpG- containing DNA stretches depending on the intended use of the pharmaceutical composition. Additionally, within the scope of this invention are pharmaceutical compositions as described hereinabove which comprise further agents which are used in treatment of viral infections, hepatopathies, inflammatory diseases or proliferative disorders, like cancer. In a preferred embodiment, the pharmaceutical composition of the present invention is a vaccine. Vaccines may be prepared, inter alia, from one or more (poly)peptides, derivatives of the (poly)peptides, nucleic acid molecules, mosaic polypeptides, fusion proteins, viruses, non-pathogenic/attenuated derivatives of the viruses, antibodies, fragments of said antibodies, derivatives of the antibodies or aptamers or other receptors of the invention. For example, nucleic acid molecules of the invention may be used for gene vaccination or as DNA vaccines. Routes for administration of gene vaccines are well known in the art and DNA vaccination has been successfully used to elicit alloimmune, anti-tumor and antiidiotype immune responses (Tighe M. et al., Immunology Today 19 (1998), 89-97). Moreover, inoculation with nucleic acid molecules/DNA has been found to be protective in different modes of viral disease (Fynan, E.F. et al, Proc. Natl. Acad. Sci. U.S.A. 90 (1993), 1 1478-1 1482; Boyer, I.D.; Nat. Med. 3 (1997), 526-532; Webster, R.G. et al., Vaccine 12 (1994), 1495-1498; Montgomery et al., DNA Cell Biol. 12 (1993), 777-783; Barry, Nature 311 (1995), 632-635; Xu and Liew, Immunology 84 (1995), 173-176; Zhoug, Eur. J. Immunol. 26 (1996), 2749-2757; Luke, J. Inf. Dis. 175 (1997), 91-97; Mor, Biochem. Pharmacology 55 (1998), 1151-1153; Donelly, Annu. Rev. Immun. 15 (1997), 617- 648; MacGregor, J. Infect. Dis. 178 (1998), 92-100). The (poly)peptides, derivatives of the (poly)peptides, fusion proteins comprising the (poly)peptide, or the mosaic polypeptide of the invention used in a pharmaceutical composition as a vaccine may be formulated e.g. as neutral or salt forms. Pharmaceutically acceptable salts, such as acid addition salts, and others, are known in the art. Vaccines can be, inter alia, used for the treatment and/or the prevention of an infection with the virus of the present invention and are administered in dosages compatible with the method of formulation, and in such amounts that will be pharmacologically effective for prophylactic or therapeutic treatments. Preferably, the vaccine comprises an attenuated viral agent as described herein above. A vaccination protocol can comprise active or passive immunization, whereby active immunization entails the administration of an antigen or antigens (like, for example, the virus/viral agent, the (poly)peptides, the derivatives of the (poly)peptides, the fusion proteins, the mosaic polypeptides and/or the nucleic acid molecules of the present invention) to the host/patient in an attempt to elicit a protective immune response. Passive immunization entails the transfer of preformed immunoglobulins or fragments thereof (for example, the above antibodies, the derivatives or fragments thereof) or the aptamers of the present invention to a host/patient. Principles and practice of vaccination and vaccines are known to the skilled artisan, see, for example, in Paul, "Fundamental Immunology" Raven Press, New York (1989) or Cryz, S. J., "Immunotherapy and vaccines", VCH Verlagsgessellschaft (1991). Typically, vaccines are prepared as injectables, either as liquid solutions or suspensions; solid forms suitable for solution in or suspension in liquid prior to injection also may be prepared. The preparation may be emulsified or the protein may be encapsulated in liposomes. The active immunogenic ingredients often are mixed with pharmacologically acceptable excipients which are compatible with the active ingredient. Suitable excipients include but are not limited to water, saline, dextrose, glycerol, ethanol and the like; combinations of these excipients in various amounts also may be used. The vaccine also may contain small amounts of auxiliary substances such as wetting or emulsifying reagents, pH buffering agents, and/or adjuvants which enhance the effectiveness of the vaccine. For example, such adjuvants can include aluminum hydroxide, N-acetyl-muramyl-L-threonyl-D- isoglutamine (thr-DMP), N-acetyl-nomuramyl-L-alanyl-D-isoglutamine (CGP 11687, also referred to as nor-MDP), N-acetylmuramyul-L-alanyl-D-isoglutaminyl-L-alanine- 2-(1 '2'-dipalmitoyl-sn-glycero-3-hydroxphaosphoryloxy)-ethylamine (CGP 19835A, also referred to as MTP-PE), and RIBI (MPL + TDM + CWS) in a 2% squalene/Tween-80® emulsion. The vaccines usually are administered by intravenous or intramuscular injection. Additional formulations which are suitable for other modes of administration include suppositories and, in some cases, oral or nasal formulations. For suppositories, traditional binders and carriers may include but are not limited to polyalkylene glycols or triglycerides. Oral formulation include such normally employed excipients as, for example, pharmaceutical grades of mannitol, lactose, starch, magnesium stearate, sodium saccharine, cellulose, magnesium carbonate and the like. These compositions may take the form of solutions, suspensions, tables, pills, capsules, sustained release formulations or powders and contain about 10% to about 95% of active ingredient, preferably about 25% to about 70%. DNA vaccines can be administered by biolistic methods, such as particle bombardment. Vaccines are administered in a way compatible with the dosage formulation, and in such amounts as will be prophylactically and/or therapeutically effective. The quantity to be adminstered generally is in the range of about 5 micrograms to about 250 micrograms of antigen per dose, and depends upon the subject to be dosed, the capacity of the subject's immune system to synthesize antibodies, and the degree of protection sought. Precise amounts of active ingredient required to be administered also may depend upon the judgment of the practitioner and may be unique to each subject. The vaccine may be given in a single or multiple dose schedule. A multiple dose is one in which a primary course of vaccination may be with one to ten separate doses, followed by other doses given at subsequent time intervals required to maintain and/or to reinforce the immune response, for example, at one to four months for a second dose, and if required by the individual, (a) subsequent dose(s) after several months. The dosage regimen also will be determined, at least in part, by the need of the individual, and be dependent upon the practitioner's judgment. It is contemplated that the vaccine containing the immunogenic compounds of the invention may be administered in conjunction with other immunoregulatory agents, for example, with immunoglobulins or with cytokines. Moreover, the present invention relates to a method of detecting the presence of the virus or viral agent in a sample comprising (a) hybridizing DNA from said sample with the nucleic acid molecule of the invention or the vector of the invention under stringent conditions; and (b) detecting the formation of a nucleic acid hybrid. Still another embodiment of the invention is a method of detecting the presence of the virus or viral agent of the invention in a sample comprising (a) hybridizing DNA from a sample with a pair of primers of the invention; (b) carrying out a PCR or another DNA amplification technique; and (c) detecting the formation of a specific PCR or another amplification product. Said primers may be of any length which allows stable hybridization to said DNA under suitable conditions (as defined herein above). In a preferred embodiment, said pair of primers comprise primers selected from the group consisting of the sequence(s) as defined in SEQ ID NO: 11 , SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 32, SEQ ID NO: 41 , SEQ ID NO: 42, SEQ ID NO: 71 , SEQ ID NO: 73, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101 , SEQ ID NO: 102, SEQ ID NO: 115, SEQ ID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, SEQ ID NO: 131 , SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 136, SEQ ID NO: 172, SEQ ID NO: 173, SEQ ID NO: 174, SEQ ID NO: 175, SEQ ID NO: 176 or SEQ ID NO: 203, SEQ ID NO: 204 or SEQ ID NO. 205. In a particular preferred embodiment, these pairs of primers comprise the sequences as defined in SEQ ID NO: 41 and SEQ ID NO: 42, in SEQ ID NO: 115 and SEQ ID NO: 71 , in SEQ ID NO: 126 and SEQ ID NO: 127, in SEQ ID NO: 128 and SEQ ID NO: 71 , in SEQ ID NO: 172 and SEQ ID NO: 71 and/or in SEQ ID NO: 174 and SEQ ID NO: 175. Suitable further DNA amplification techniques are known in the art and comprise, inter alia, Ligase Chain reaction, Strand Displacement Amplification, Nucleic Acid Sequence based Amplification (NASBA), or Q-beta replicase based techniques. Preferably, hybridization (and subsequent washing) is effected under stringent conditions; see, e.g., Sambrook et al., loc. cit. Furthermore, the invention relates to a method of detecting the presence of the virus of the invention in a sample comprising (a) incubating said sample with the antibody or fragment or derivative or an aptamer or other receptor of the invention; and (b) detecting the formation of a complex between a (poly)peptide or virus or viral agent present in said sample and said antibody or fragment or derivative thereof or said aptamer or other receptor. Additionally, the invention relates to a method for detecting the antibody or fragment or derivative thereof or an aptamer or other receptor of the invention in a sample, comprising (a) incubating said sample with the nucleic acid molecule of the invention, the virus the invention or the (poly)peptide of the invention or fragments thereof or with the derivative of the (poly)peptide of the invention, and (b) detecting the formation of a complex between said antibody, said fragment or said antibody derivative or said aptamer or other receptor and said nucleic acid molecule, said virus or said (poly)peptide or said fragments or derivatives. Detection per se in the above recited method can be done according to conventional protocols. For example, hybridized or amplified DNA can be detected in a gel, for example, by reference to the molecular weight of the nucleic acid molecule, by using anti-double strands antibodies or by detecting proteinaceous complexes formed with secondary antibodies. Other options for the detection step are immediately apparent to the person skilled in the art. Suitable formats for the detection step comprise ELISAs, RIAs and the like. Methods of detection of viruses/viral infections are well known in the art and comprise, besides immunoassays, microscopy techniques, like immunodetections in light- and electron-microscopy (see, for example, Fields "Virology" 3 rd edition, Lippincott-Raven (1996); Evans A. S., "Viral Infections of Humans" (1989), Plenum Publishing Corporation). In yet a more preferred embodiment, the invention relates to a method as described above, wherein said nucleic acid molecules, at least one of said primers or said antibody or fragment or derivative thereof or aptamer or other receptor is detectably labeled. Such labels are well known to the person skilled in the art, have been referred to herein above, and may comprise a tag, a fluorescent marker or a radioactive marker. Any detection method for detecting the presence of the virus of the invention or the presence of antibodies generated against the virus of the invention (an embodiment described herein before) may be assisted by computer technology. Detection methods can therefore be automated by various means, including image analysis or flow cytometry. For a further understanding of markers and preferred embodiments thereof, it is referred to corresponding passages herein above. Furthermore, the present invention relates to a method as described above wherein said sample is or is derived from blood, serum, sputum, feces or another body fluid. The sample to be analyzed may be treated such as to extract, inter alia, nucleic acid molecules, (poiy)peptides, or antibodies. In yet another embodiment, the present invention relates to a preparation of substantially isolated polyclonal antibodies specifically immunoreactive with the nucleic acid molecule, the (poly)peptide of the invention or the virus of the invention. How to obtain such a preparation of polyclonal antibodies is well known to the artisan and can be carried out without any undue experimentation (see Harlow and Lane, loc. cit.). Said polyclonal antibodies may be monospecific or polyspecific. Furthermore, the present invention relates to a method of producing antibodies to the nucleic acid molecule, the (poly)peptide, the derivative or the virus of the invention comprising immunizing an experimental animal with said nucleic acid, (poly)peptide, derivative, virus/viral agent or the non-pathogenic derivative of the invention and isolating serum or specific antibodies produced. The antibody obtained from the animal may be further manipulated, e.g., cleaved to obtain suitable fragments or may be the starting compound for genetically engineered antibodies or derivatives thereof, such as scFv fragments having the same binding specificity. Alternatively, it may be the starting compound for the production of corresponding synthetic compounds manufactured, for instance, by peptidomimetics. The production of antibodies is well known in the art. Such antibodies may include, but are not limited to, polyclonal, monoclonal, chimeric, single chain, antibodies or fragments such as Fab fragments, and fragments produced by a Fab or scFv expression library. For the production of antibodies in experimental animals, various hosts including goats, rabbits, rats, mice, and others, may be immunized by injection with nucleic acids, (mosaic) polypeptides of the present invention or any fragment or oligopeptide or derivative thereof which has immunogenic properties or forms a suitable epitope. Alternatively (attenuated) virus/viral agent or derivatives thereof may be used for immunization. Techniques for producing and processing polyclonal antibodies are known in the art and are described in, among others, Mayer and Walker, eds., "Immunochemical Methods in Cell and Molecular Biology", Academic Press, London (1987). Polyclonal antibodies also may be obtained from an animal, preferably a mammal, previously infected with the virus of the invention. Methods for purifying antibodies are known in the art and comprise, for example, immunoaffinity chromatography. Depending on the host species, various adjuvants or immunological carriers may be used to increase immunological responses. Such adjuvants include, but are not limited to, Freund's, complete or incomplete adjuvants, mineral gels such as aluminium hydroxide, and surface active substances such as lysolecithin, pluronic polyols, polyanions, peptides, oil emulsions and dinitrophenol. An example of a carrier, to which, for instance, a peptide of the invention may be coupled, is keyhole limpet hemocyanin (KLH). It is preferred that the (mosaic) (poly)peptides, fragments, or oligopeptides, derivatives used for the production of antibodies have an amino acid sequence consisting of at least five amino acids, such as six, seven, eight or nine and more preferably at least 10 amino acids and most preferably at least 15 amino acids. It is also preferable that they are identical to a portion of the amino acid sequence of a natural protein, and they may contain the entire amino acid sequence of a small, naturally occurring molecule. Short stretches of (poly)peptides or fragments thereof of the invention may be fused with those of another protein such as keyhole limpet hemocyanin and antibody may be produced against the chimeric molecule. This includes specific antibodies to the (poly)peptide of the invention. A different strategy would be to couple the short peptides as haptens to a carrier such as KLH or BSA using conventional methods and immunizing the animals with such immunoconjugates. In another embodiment, the present invention relates to a method of immunizing an individual against the virus or viral agent of the invention, preferably SEN viruses comprising administering to said individual at least one dose of the vaccine of the invention. Said individual is preferably a human. Preferred is to give the individual at least one boost injection, such as one, two or three boost injections. With respect to the routes, doses and time intervals, it is referred to previous passages in this specification. In a further embodiment, the invention relates to a method of propagating the virus/viral agent of the invention comprising culturing the host cell of the invention under conditions suitable to promote the propagation of said virus. Viral propagation methods are generally known in the art (see, e.g., Fields, "Virology", 3 rd ed., 1996, Lippincott Raven Publishers, Philadelphia) and can be adapted by the person skilled in the art using or adapting routine experimentation. In yet another embodiment, the invention relates to a method of propagating the virus of the invention in an animal comprising inoculating said animal with said virus, part(s) of said virus and/or material infected by said virus. The replication of said virus can be monitored in the blood or in various organs. Infected cells can be isolated and these cells can be utilized for viral preparations. Animal models used for viral preparations and for virus propagations are well known in the art and comprise, but are not limited to, mice, rats, rabbits, guinea pigs, ducks, cats, dogs, chimpanzees, marmosets. Additionally, the present invention relates to the use of an anti-viral agent for the preparation of a pharmaceutical composition for the treatment of a disease which is related to and/or caused by the virus or viral agent of the invention. Said disease is preferably selected from the group consisting of hepatopathies, inflammatory diseases and proliferative disorders. Antiviral agents are well-known in the art and comprise, inter alia, interferons (like interferon alpha) or drugs like tribavirin, lamivudine, aciclovir and/or ursodeoxycholic acid. Other compounds used in the treatment of viral infections comprise amantadine hydrochloride, cytarabine and levamisole hydrochloride (see, e.g., Martindale; "The Extra Pharmacopeia"; The Royal Pharm. Soc, London, 1996). In yet another embodiment, the invention relates to the use of the antibody or fragment or derivative thereof or an aptamer or other receptor of the invention for the preparation of a pharmaceutical composition for the treatment or a disease which is related to and/or caused by the virus or viral agent of the invention, preferably for the treatment of hepatopathies, inflammatory diseases and/or proliferative disorders. Said hepatopathy can be, inter alia, acute or chronic hepatitis of unknown etiology (NANE-hepatitis), said inflammatory disease may be Crohn's disease or Lupus erythematosus and said proliferative disorder comprises cancer, like, inter alia, liver or colon cancer (liver or colon carcinomas). Finally, the invention relates to methods of treating or preventing a disease in a mammal, preferably a human that is afflicted with the virus/viral agent of the invention comprising administering to said mammal one or more doses of an anti-viral agent, antibody, fragment or derivative thereof, aptamer or other receptor, all as described before. Preferably, diseases to be treated with the method of the invention have also been identified before. The regimen of administration are preferably conventional uses as have been described hereinbefore. The above compound(s) may be administered together with further medicaments optionally directed to further etiologic agents. Throughout this specification and the claims which follow, unless the context requires otherwise, the word "comprise", and variations such as "comprises" and "comprising", will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integer or step. The figures show: Figure 1 PCR products obtained with primers TTV-1 and NG063 using DNA extracted from the sera of the indicated patients as template. The arrows indicate the size of the bands obtained. Figure 2 Alignment of nucleic acid sequences obtained with primers TTV-1 and NG063 from patients SEN, 37 and 28. Identical bases are indicated by asterisks. Figure 3 Alignment of nucleic acid sequences obtained with primers TTV-1 and NG063 from patients SEN and patient 26. Identical bases are indicated by vertical lines. Figure 4 Alignment of the translated sequences obtained with primers TTV-1 and NG063 from patients SEN, 37, 28 and 26. Conserved residues are indicated by asterisks. Figure 5 Gene walking poiymerase chain reaction strategy for sequence extension. PCR products obtained with DNA extracted from the sera of patient SEN and from an healthy blood donors with primers NG063 and CWP. The 1200 bp bands obtained with DNA extracted from patient SEN is indicated by the arrow. Figure 6 Alignment of the TTV ORF1 sequence with the translated CWP SEN 001 sequence derived from patient SEN. Identical residues are indicated by vertical bars. Gaps were introduced for optimizing the alignment. Figure 7 DNA Enzyme Immuno Assay (DEIA) analysis of PCR products obtained with primers 3S and 2AS using DNA obtained from patient SEN (sample 1) and from 37 healthy blood donors (samples 2-38). Ten μl of PCR product were hybridized with biotinilated probe SEN 37 in a microwell plate and the bound material was revealed as previously described with a colorimetric method. Figure 8 DNA Enzyme Immuno Assay (DEIA) analysis of PCR products obtained with primers 3S and 2AS using DNA obtained from 41 intravenous drug addicts subjects. Ten μl of PCR product were hybridized with biotinilated probe SEN 37 in a microwell plate and the bound material was revealed as previously described with a calorimetric method. Figure 9 Alignments of sequences NAE8-1 , NAE35-5, NAE9-3 and NAE10-4 obtained by PCR with primers 2AS and 3S from four patients suffering from hepatitis of unknown etiology. Figure 10 Alignment of sequence CWPSEN001 and sequence NAE8-1. Identical nucleotides are indicated with vertical bars. Figure 11 Alignment of sequence CWPSEN001 and sequence NAE9-3. Identical nucleotides are indicated with vertical bars. Figure 12 Alignment of sequence CWPSEN001 and sequence NAE10-4. Identical nucleotides are indicated with vertical bars. Figure 13 Alignment of sequence CWPSEN001 and sequence NAE35-5. Identical nucleotides are indicated with vertical bars. Figure 14 Alignment of the CWPSEN 001 and SENV-B nucleotide sequences. Identical nucleotides are indicated with vertical bars. Figure 15 Alignment of the CWPSEN 001 and SENV-B deduced amino acid sequence. Identical residues are indicated with vertical bars. Figure 16 Alignment of the deduced amino acid sequence of ORF 1 of TTV and of ORF 1 of SENV. Identical residues are indicated with vertical bars. Figure 17 Nucleotide sequence of SENV-A and its translation ain the three reading frames. Figure 18 Alignment of the SENV-A and TTV1 nucleotide sequences. Identical nucleotides are indicated with vertical bars. Figure 19 Alignment of the nucleotide sequences according to major ORFs of SENV-A and of TTV. Identical nucleotides are indicated with vertical bars. Figure 20 Alignment of the predicted amino acid sequences encoded by the main coding regions of TTV and SENV-A sequences. Identical residues are indicated with vertical bars. Figure 21 Alignment of the deduced protein sequences of ORF2 of TTV and ORF2 of SENV-A. Identical residues are indicated by vertical bars. Figure 22 Alignment of the nucleotide sequences encoding SENV-A and SENV-B. Bold characters indicate the initiator and terminator codons of the three different open reading frames (ORFs). Figure 23 Alignment of the deduced ORF 1 protein sequences of SENV-A and SENV-B. Figure 24 Alignment of the deduced ORF 1 protein sequences of SENV-B and TTV. Figure 25 Alignment of the deduced ORF 2 protein sequences of SENV-A and SENV-B. Figure 26 Alignment of the deduced ORF 3 protein sequences of SENV-A and SENV-B. Figure 27 Alignment of the nucleotide sequences encoding SENV-A and SENV-B (ORF1 region). Figure 28 Alignment of the nucleotide sequences encoding SENV-A and SENV-B (ORF2 region). Figure 29 Alignment of the nucleotide sequences encoding TTV and SENV-B (ORF1 region). Figure 30 Alignment of the nucleotide sequences encoding TTV and SENV-B (ORF2 region). Figure 31 Alignment of the deduced protein sequences encoded by the DNA fragments amplified with primers L1 S and L3AS. Conserved amino acids are indicated with asterisks. Figure 32 Unrooted phylogenic tree derived from alignments of deduced protein sequences encoded by the DNA fragments amplified with primers L1A and L3AS. The most homologous region of TTV and SENV-A, as well as a random sequence derived from HGV have been included in the a analysis. Figure 33 Alignment of the deduced ORF 1 protein sequences of SENV-A and SENV-C. Figure 34 Alignment of the deduced ORF 1 protein sequences of SENV-B and SENV-C. Figure 35 Alignment of the deduced ORF 1 protein sequences of SENV-C and TTV. Figure 36 Alignment of the deduced ORF 2 protein sequences of SENV-C and SENV-A. Figure 37 Alignment of the deduced ORF 2 protein sequences of SENV-C and SENV-B. Figure 38 Alignment of the deduced ORF 2 protein sequences of SENV-C and TTV. Figure 39 Alignment of the deduced ORF 3 protein sequences of SENV-C and SENV-A. Figure 40 Alignment of the deduced ORF 3 protein sequences of SENV-C and SENV-B. Figure 41 Alignment of the nucleotide sequences encoding SENV-C and SENV-A (ORF1 region). Figure 42 Alignment of the nucleotide sequences encoding SENV-C and SENV-B (ORF1 region). Figure 43 Alignment of the nucleotide sequences encoding TTV and SENV-C (ORF1 region). Figure 44 Alignment of the ORF 2 nucleotide sequences encoding SENV-C and SENV-A. Figure 45 Alignment of the ORF 2 nucleotide sequences encoding SENV-C and SENV-B. Figure 46 Alignment of the ORF 2 nucleotide sequences encoding SENV-C and TTV. Figure 47 Alignment of the ORF 3 nucleotide sequences encoding SENV-C and SENV-A. Figure 48 Alignment of the ORF 3 nucleotide sequences encoding SENV-C and SENV-B. Figure 49 Analysis of the percentage of nucleotide identity between the indicated sequences. Figure 50 Analysis of the percentage of amino acid identity between the indicated sequences. Figure 51 Phylogenic distances calculated on the basis of the alignments of the indicated amino acid sequences. Figure 52 Unrooted phylogenic tree derived from alignments of deduced ORF 1 protein sequences of SENV-A, SENV-B, SENV-C and TTV Figure 53 Presence of SENV in clinical samples. Figure 54 Optical density values obtained with DNA extracted from indicated clinical samples and amplified with SENV specific primers. Figure 55 Phylogenetic distances calculated for the different SENV-ORF1 protein sequences Figure 56 Percentage of SENV-A positive samples among different groups of patients. The numbers in brackets indicate the number of patients analyzed for each group. Figure 57 Percentage of SENV-B positive samples among different groups of patients. The numbers in brackets indicate the number of patients analyzed for each group. Figure 58 Percentage of SENV-C positive samples among different groups of patients. The numbers in brackets indicate the number of patients analyzed for each group. Figure 59 Percentage of SENV-D positive samples among different groups of patients. The numbers in brackets indicate the number of patients analyzed for each group. Figure 60 DNA extracted from serum samples which are positive for either SENV- A, SENV-B, SENV-C or SENV-D were tested with reaction 1 , reaction 2 or reaction 3 (For detailed information on the three different reactions see example 20). The data are expressed as optical values of a DEIA assay. Positive values are indicated in bold. Figure 61 Western blot of recombinant SENV-A ORF2 protein (30k mw) .Western blot with serum ID 2174 (dil. 1 :100), tracer anti-human IgG-HRP (dil. 1 :500). Lane 1 : Low Molecular Weight Marker; Lane 2: Loaded ORF2; Lane 3: Flow Through; Lane 4: Pool 4-1 1 ; Lane 5: Pool 19-25; Lane 6: Pool 33- 39; Lane 7: Pool 48-54; Lane 8: Pool 61-64. Figure 62 Prevalence of different SENV subtypes among different, indicated chorts of patients. Figure 63 Cumulative prevalence of SENV-C and SENV-D subtypes among the indicated cohorts of patients. Figure 64 Comparative analysis of the percentage of identities at the amino acid level of the different ORFs. Alignment were obtained using the PALIGN program of the PCGENE package using the following parameters: Open Gap Cost: 10 and Unit Gap Cost: 2. Figure 65 Comparative analysis of the percentage of identities at the nucleotide level of the different ORFs. Alignment were obtained using the NALIGN program of the PCGENE package using the following parameters: Open Gap Cost: 100 and Unit Gap Cost: 10. Figure 66 Detection of HIV and SENV viremia in a patient undergoing HAART therapy. HIV viremia (squares) is indicated as number of virions/ml; SENV viremia (dots) is indicated as optical density value Figure 67 Detection of SENV in peripheral blood cells of 4 positive (right hand bars, labelled "+") and 4 negative patients (left hand bars, labeled "-"). The data are expressed as optical density values. Figure 68 Detection of SENV in the supernatant of PBC culture. PBC from a SENV positive patient were cultured for 5 days in the presence of PHA. Supernatant fractions were collected at the indicated days and tested for SEN presence. The data are expressed as optical density values. Figure 69 Detection of SENV RNA in liver tissue. Reactivities of PCR products obtained with SENV primers using RNA and cDNA derived from neoplastic (TT) and peritumoral (TS) surgical liver tissues obtained from 2 hepatocarcinoma patients. Figure 70 Map of the clones deposited with DSMZ, Mascheroder Weg 1 b, D- 38124 Braunschweig, GERMANY. Bold lines represent the non-coding nucleotide sequences conserved among TTV and all the SEN viruses. The invention will now be described by reference to the following biological examples which are merely illustrative and are not to be construed as a limitation of scope of the invention. Example 1 Estimation of prevalence and diversity of TTV in the Italian population using specific TTV primers Following the discovery of TTV Nishizawa, Hepatology Res 10 (1998), 1 -16, the prevalence and the diversity of this viral agent in the Italian population was studied. The nested PCR method originally described by Okamoto et al., Hepatology Res 241 (1998), 1 -16 was used under the employment of the sense primers NG059 and NG061 and anti-sense primer NG063 as defined in Okamoto et al., loc. cit. PCR was performed with a 50-μl mixture containing template, 1/10 th of DNA extracted from 100 μl of serum with QIAamp blood kit (QIAGEN), PCR buffer (67 mM Tris HCI pH 8.8, 16.6 mM (NH 4 ) 2 S0 4 , 10mM β-mercaptoethanol, 1.5 mM MgCI 2 ), 300 ng of each PCR primer, 200 μM deoxyribonucleoside triphosphates (dATP, dCTP, dTTP and dGTP from Boehringer, Mannheim, Germany), and 1.25 U of Taq polymerase (Perkin Elmer). The reaction was performed in a DNA thermal cycler with mineral oil. PCR consisted of a preheating at 94°C for 5 min, 45 cycles of 94°C for 1 min, 55°C for 1 min, and 72°C for 1 min, and an incubation at 72°C for 7 min. The PCR products were loaded on a 2% agarose gel with 2 μg of ethidium bromide per ml to determine the sizes of the amplified products. With these primers, TTV was detected in 10% of intravenous drug users and in only 1% of blood donors healthy controls Samples were obtained from the Transfusion Unit of the Ospedale Civile of Brescia, Italy. DNA sequencing analysis was carried out in 10 TTV-positive samples which verified that these amplicons represented the TTV genome. Furthermore, this analysis revealed a great degree of variability between the different italian TTV isolates. Example 2 Single step PCR for the estimation of prevalence and diversity of TTV in the Italian population Considering the level of variability and the low incidence of infection detected with TTV-specific primers as described in Example 1 , a new single step PCR method was developed. The PCR primers used in this assay were NG063 anti-sense Okamoto et al., loc. cit. and primer sense TTV-1 S, deduced on the basis of sequences found in the Italian population. The sequence of primer TTV-1 S was: 5ΑCACCTGGTACAGRGGAACAGYATATA3', wherein R = A or G and Y = C or T (SEQ ID NO: 1 ). PCR was performed with a 50-μl mixture containing template, 1/10 th of DNA extracted from 100 μl of serum with QIAamp blood kit (QIAGEN), PCR buffer (67 mM Tris HCI pH 8.8, 16.6 mM (NH 4 ) 2 S0 4 , 10mM β-mercaptoethanol, 1.5 mM MgCI 2 ), 300 ng of each PCR primer, 200 μM deoxyribonucleoside triphosphates (dATP, dCTP, dTTP and dGTP from Boehringer, Mannheim, Germany), and 1.25 U of Taq polymerase (Perkin Elmer). The reaction was performed in a DNA thermal cycler with mineral oil. PCR consisted of a preheating at 94°C for 5 min, 45 cycles of 94°C for 1 min, 50°C for 1 min, and 72°C for 1 min, and an incubation at 72°C for 7 min. The PCR products were loaded on a 2% agarose gel with 2 μg of ethidium bromide per ml to determine the sizes of the amplified products. Negative controls containing ail of the reagents but lacking template DNA were routinely processed exactly as described above to monitor for contamination and were negative in all experiments. With the above described single step PCR, TTV infection was detected in 55% of intravenous drug users and in 13% of blood donors, confirming therefore the high incidence of this viral agent in the normal population. Example 3 Isolation and characterization of different PCR products PCR was carried out on samples derived from intravenous drug users as described in Example 2, supra. In contrast to the 513 bp PCR product, expected for TTV positive samples, it was observed that the amplicons derived from two intravenous drug users (sample SEN and LIM) had a length of 580 bp. Furthermore the PCR product of two intravenous drug users contained both fragments of 513 bp and 580 bp (Fig. 1). In order to determine the nature of the differently sized bands, amplicons containing poly A tails were excised from the agarose gel and the DNA content was purified and ligated to a pGEM vector (Promega, Madison, WI, USA). Using DNA extracted from with the different obtained PCR products transformed E. coli, both strands were sequenced with AutoRead sequencing Kit (Pharmacia Biotech) using fluorescent M13 Universal Primer and fluorescent M13 Reverse Primer (Pharmacia Biotech, Sweden). Sequences were determined on three clones each for respective PCR products and the consensus sequence was adopted. This analysis revealed that the sequence of the 513 bp amplicons were between 85% to 98% identical to the TTV-1 isolates contained in the GENEBANK database (Accession number: AB008394). The sequence of 580 bp derived from the patient SEN (clone SEN 8001 ; SEQ ID NO: 2), however, did not have any high homology with any of the sequences deposited in the GENEBANK data base using BLASTN, BLASTP and FASTA programs. The highest homology at the nucleotide level (48%) was detected with some stretches of the TTV sequence, suggesting that the SENV genome encodes for a new virus distantly related to TTV. An ORF capable of encoding 187 amino acids (SEQ ID NO: 3) was recognized in sequence SEN 8001 in a reading frame starting at the second nucleotide. No further ORF in the other two reading frames starting at the first or third nucleotide, or in any of the three reading frames in the complementary sequence which could code for > 100 amino acids could be deduced. The amino acid sequence of this ORF had no significant homology with any of the protein sequences contained in the database (GENEBANK) and had only 32 % of homology with the ORF encoded by the TTV sequence. The 581 bp amplicon derived from two additional intravenous drug users (clones N37 (SEQ ID NO: 4) and N28 (SEQ ID NO: 5)) had a sequence that was 95 % homologous to the one derived from patient SEN, demonstrating that this viral agent is present in different individuals and that is rather conserved. The alignment of clone SEN8001 and the clones N37 (SEQ ID NO: 4) and N28 (SEQ ID NO: 5) is documented in Fig. 2. Example 4 Characterization of a SEN-Virus subtype Clone 26 A (SEQ ID NO: 6) was derived from an intravenous drug user whose amplicon seemed to migrate slightly slower than the 580 band detected in patient SEN. Fig. 3 shows the alignment of sequence SEN8001 with the one obtained from clone 26A. The homology between the two clones was 81 %, furthermore clone 26A contained an insertion of 15 nucleotides. Thus clone 26A (SEQ ID NO: 6) encodes for a subtype of SENV. At the protein level clone 26A had 76 % of homology with clone SENV and, as expected, an insertion of a stretch of 5 amino acids (SEQ ID NO: 7). Fig. 4 shows the alignment between the ORFs encoded by clones SEN8001 , N37, N28 and 26A. Example 5 Extension of the SEN-virus genome by targeted gene walking PCR in order to extend the sequence of the SENV genome, the "targeted gene walking polymerase chain reaction" strategy was used, as originally described by Parker et al., Nuc. Ac. Research 19 (1991), 3055-60. The method is based upon the observation that a primer may initiate PCR at either unknown or specific target sequences which bear only partial homology at the 3' end. The technique can be used to "walk" along the DNA sequence or to search for nucleotide sequences that have been designed by the user. The method allows the production of micrograms of DNA of unknown sequences that occur upstream or downstream from a single region of targeted DNA. For this approach a series of PCR reaction all containing the same NG063 targeted primer as used in Example 2 were set up. As "walking primer" (one in each different PCR reaction) oligonucleotides that had been previously synthesized for various different target amplifications were utilized. The primers used in these experiments were derived from sequences of the human T-cell receptor, from hepatitis G virus, from hepatitis B virus and from hepatitis C virus. The most useful primer was the primer denoted CWP, as described below. For each couple of primers, duplicate PCR reactions, one containing DNA extracted from positive sample and the other one containing DNA extracted from negative blood donor were set up. PCR was performed with a 50-μl mixture containing template, 1/10 th of DNA extracted from 100 μl of serum with QIAamp blood kit (QIAGEN), PCR buffer (67 mM Tris HCI pH 8.8, 16.6 mM (NH ) 2 S0 4 , 10mM β- mercaptoethanol, 1.5 mM MgCI 2 ), 300 ng of each PCR primer, 200 μM deoxyribonucleoside triphosphates (dATP, dCTP, dTTP, dGTP from Boehringer, Mannheim, Germany), and 1.25 U of Taq polymerase (Perkin Elmer). The reaction was performed in a DNA thermal cycler with mineral oil. PCR consisted of a preheating at 94°C for 5 min, 50 cycles of 94°C for 1 min, 60°C for 1 min, and 72°C for 1 min, and an incubation at 72°C for 7 min. The PCR products were loaded on a 2% agarose gel with 2 μg of ethidium bromide per ml to determine the sizes of the amplified products. Only bands that were present in the positive sample and absent in the reaction containing the negative sample were excised from the agarose gel, cloned and sequenced. Most of the clones contained genomic DNA, however, upon sequencing, one band of 1200 bp (Fig.5 (SEQ ID NO: 8)) obtained with primers NG063 (Okamoto et al., loc. cit.) and CWP 5'CGCCTGRTANARNGGCCARCA 3' (SEQ ID NO: 178) was found to contain the SENV sequence extended of 700 bases in 5' (clone CWP SEN 001 ; SEQ ID NO: 8). The CWP primer (SEQ ID NO: 178) was derived from the non-structural region of hepatitis G virus 600 bp from the 5' region of the genome, wherein R = A or G and N = A, C, G or T. To extend the sequence in 3' the "targeted gene walking strategy" was employed. However, instead of using two primers, only the primer 3S (5'TCC ATA TTC ATA GGC CCC AA3' SEQ ID NO: 11 ) derived from the sequence SEN8001 was utilized. By using this strategy, a clone containing the SENV sequence extended of 200 bases in 3' was obtained. After assembling the overlapping sequences with the ASSEMLGEL program of the PC-GENE package an unique sequence of 1353 bases encoding for part of the SENV genome was obtained. This sequence was named CWP SEN001 (SEQ ID NO: 9). Database analysis with BLAST program did not reveal any major homology with known sequences and, again, the closest homology (46,93%) was found with TTV. An ORF capable of encoding 450 amino acids was recognized in a reading frame starting at the third nucleotide of sequence CWPSEN001 (SEQ ID NO: 10). No ORF in the other two reading frames starting at the first or third nucleotide, or in any of the three reading frames in the complementary sequence which could code for > 100 amino acids was found. The amino acid sequence of this ORF had not significant homology with any of the protein sequences contained in the database (GENEBANK). The greatest global sequence identity (29.4%) was detected between the SENV ORF (SEQ ID NO: 10) and TTV (Fig. 6). As comparison, it is to note that the identity between the polyproteins of HGV and GBV-A is 43.8%, whereas the identity of HGV with GVB-B and the HCV-1 isolate of HCV is 28.4 and 26.8, respectively (Linnen, Science 271 (1996), 505-508). According to PROSITE prediction, the SENV ORF characterized contains two potential N-glycosylation sites at positions 54 and 233, one thyrosine sulfatation site at position 160, three potential protein kinase C phosphorylation sites at positions 89, 235 and 431 , four potential casein kinase II phosphorylation sites at positions 119, 161 , 315 and 319 and two potential amidation sites at positions 83 and 228. N-Myrisoylation sites were not detected. In comparison, the region of highest homology with SENV of the TTV ORF 1 (Fig. 6) contained 4 N-glycosilation sites at positions 175, 191 , 206 and 234, one tyrosine sulfatation site at position 275, seven protein kinase C phosphorylation sites at positions 77, 99, 158, 207, 223, 311 and 325, eight casein kinase II phosphorylation sites at positions 17, 119, 144, 158, 232, 271 , 294 and 359, one tyrosine kinase phosphorylation site at position 103, seven N-myrisoylation sites at positions 128, 190, 195, 240, 267, 281 and 282 and one amidation site at position 82. In respect to the BLAST search and the sequence-analysis detection of sites, regions and signatures of potential biological interest, the results demonstrate that TTV and SENV are different viruses that may be distantly related. Example 6 Prevalence of SENV in the Italian population In order to obtain precise information on the prevalence of SENV in the population a specific PCR assay was developed. DNA was extracted from 100 μl of serum and subjected to 45 cycles of PCR using primer SEN 3S sense 5'TTC(A/C)ATATT(T/C)ATAGGCCCCAA3' (SEQ ID NO. 11) and primer SEN 2AS as antisense 5TCCAAARTTAGTGTCATAGAAWAC3' (SEQ ID NO: 12, wherein R = A or G and W = A or T) derived from the CWPSEN001 sequence (SEQ ID NO: 9). The PCR products were loaded on a 2% agarose gel with 2 μg of ethidium bromide per ml to determine the sizes of the amplified products. Negative controls containing all of the reagents but lacking template DNA were routinely processed exactly as described above to monitor for contamination and were negative in all experiments. In order to verify the specificity of the amplicons 20 μl of PCR products were hybridized in a DEIA assay Mantero et al., Clin. Chemistry 37 (1991), 422-429, as previously described using the SEN 37 biotinilated probe 5TAT GCC CAT ACA CAG TTC CCC CCA TGT ACA AAC CAG GCA3' (SEQ ID NO: 13) covering a region internal to the one delimited by the 3S and 2AS primers. PCR was performed with a 50-μl mixture containing template, 1/10 th of DNA extracted from 100 μl of serum with QIAamp blood kit (QIAGEN), PCR buffer (67 mM Tris HCI pH 8.8, 16.6 mM (NH 4 ) 2 S0 4 , 10mM β-mercaptoethanol, 2 mM MgCI 2 ), 300 ng of each PCR primer, 200 μM deoxyribonucleoside triphosphates (dTTP, dATP, dCTP, dGTP from Boehringer, Mannheim, Germany), and 1.25 U of Taq polymerase (Perkin Elmer). The reaction was performed in a DNA thermal cycler with mineral oil. PCR consisted of a preheating at 94°C for 5 min, 45 cycles of 94°C for 1 min, 50°C for 1 min, and 72°C for 1 min, and an incubation at 72°C for 7 min. The PCR products were loaded on a 2% agarose gel with 2 μl of ethidium bromide per ml to determine the sizes of the amplified products. Negative controls containing all the reagents but lacking DNA template were routinely processed exactly as described above to monitor for contamination and were negative in all the experiments. SENV was detected in none of the 37 blood donors (Fig. 7) and in none of the 32 patients suffering from rheumatoid arthritis tested. However, the viral agent was detected in 29 of the 41 (67%) intravenous drug users analyzed (Fig. 8). Thus, these data document the parenteral route of transmission of SENV. Example 7 SENV and SENV subtypes as pathogens involved in hepatitis of unknown ethiology To assess the possible implication of SENV in transmitting hepatitis of unknown ethiology, DNA extracted from the sera of 20 patients suffering from hepatitis nonA- nonE (negative for all markers of known hepatitis viruses) was amplified. The amplification was carried out with primers 3S (SEQ ID NO: 11 ) and 2AS (SEQ ID NO: 12). PCR was performed with a 50-μl mixture containing template, 1/10 th of DNA extracted from 100 μl of serum with QIAamp blood kit (QIAGEN), PCR buffer (67 mM Tris HCI pH 8.8, 16.6 mM (NH 4 ) 2 S0 4 , 10mM β-mercaptoethanol, 1.5 mM MgCI 2 ), 300 ng of each PCR primer, 200 μM deoxyribonucleoside triphosphates (dATP, dTTP, dCTP, dGTP from Boehringer, Mannheim, Germany), and 1.25 U of Taq polymerase (Perkin Elmer). The reaction was performed in a DNA thermal cycler with mineral oil. PCR consisted of a preheating at 94°C for 5 min, 50 cycles of 94°C for 1 min, 60°C for 1 min, and 72°C for 1 min, and an incubation at 72°C for 7 min. Nine of these amplified samples migrated in a agarose gel as a weak band of the expected 330 bp size; however these PCR products did not hybridize with the SEN 37 biotinilated probe (SEQ ID NO: 13) in a DEIA assay (Mantero et al., loc. cit.) Gel slices corresponding to two of the 330 bp bands obtained from four sera from patients with hepatitis of unknown etiology (patients NAE8, NAE 9, NAE 10 and NAE 35) were cut out, the extracted DNA was connected to a pGEM vector (Promega, Madison, WI, USA) and introduced in E. coli. The DNA sequences of the inserts, named NAE8-1 (SEQ ID NO: 14), NAE9-3 (SEQ ID NO: 15), NAE10-4 (SEQ ID NO: 16) and NAE 35-5 (SEQ ID NO: 17) , were determined by using the AutoRead sequencing Kit (Pharmacia Biotech) with fluorescent M13 Universal primer and fluorescent M13 Reverse Primer (Pharmacia Biotech). Figure 9 shows the alignments of the sequences derived from these four patients suffering from NonA-NonE hepatitis. The four sequences have 98.28% identity, suggesting that a virus encoded by this particular genome is highly prevalent in NonA-NonE hepatitis patients. Figures 10, 11 , 12 and 13, respectively, show the alignments of clones NAE8-1 and NAE9-3, NAE10-4 and NAE 35-5 with clone SEN8001. These sequences have an homology with clone SEN8001 that varies between 65,90% to 69,77%, suggesting that clones NAE8-1 NAE9-3, NAE10-4 and NAE35-5 are a new subtype of SENV that is named SENV-B. The fact that SENV-B appears to be selectively segregated in the sera of NonA-NonE patients suggests that this SENV subtype may be involved in the transmission of hepatitis of unknown hetiology. The numerous mismatches between the SEN 37 biotinilated probe and the SENV-B sequences can account for the low reactivity of the PCR products derived from NonA-NonE patients in the DEIA hybridization assay and implies that SENV-B is not a causative agent of NANE-hepatitis. In order to extend the NAE 8-1 sequence (SEQ ID NO: 14) in 5' as well as in 3', DNA extracted from the serum of patient NAE 8 was amplified with the primer NAE 2AS (SEQ ID NO: 18) derived from SEQ ID NO: 14 and primer 6S (SEQ ID NO: 19) derived from the CWPSEN 001 sequence (SEQ ID NO: 9). PCR was performed with a 50-μl mixture containing template, 1/10 th of DNA extracted from 100 μl of serum with QIAamp blood kit (QIAGEN), PCR buffer (67 mM Tris HCI pH 8.8, 16.6 mM (NH 4 ) 2 S0 4 , 10mM β-mercaptoethanol, 2 mM MgCI 2 ), 300ng of each PCR primer, 200 μM deoxyribonucleoside triphosphates (dATP, dCTP, dTTP, dGTP from Boehringer, Mannheim, Germany), and 1.25 U of Taq polymerase (Perkin Elmer). The reaction was performed in a DNA thermal cycler with mineral oil. PCR consisted of a preheating at 94°C for 5 min, 45 cycles of 94°C for 1 min, 60°C for 1 min, and 72°C for 1 min, and an incubation at 72°C for 7 min. The PCR products were loaded on a 2% agarose gel with 2 μg of ethidium bromide per ml to determine the sizes of the amplified products. A gel piece corresponding to the 1100 bp band was cut out. The DNA was extracted, cloned into a pGEM vector (Promega, Madison, WI, USA), introduced into E. Coli and sequenced using standard methods. The DNA sequence of the insert, named SENV-B (SEQ ID NO: 20), was determined, using the AutoRead sequencing Kit (Pharmacia Biotech) with fluorescent M13 Universal primer and fluorescent M13 Reverse primer (Pharmacia Biotech). Fig. 14 shows the alignment of SENV-B and the CWPSEN001 nucleotide sequences. The two sequences show 52,11% homology and the ALIGN program introduced 6 gaps in the SENV-B sequence in order to obtain the best score. The alignment of the CWPSEN001 amino acid sequence and the SENV-B predicted amino acid sequences (SEQ ID NO: 21) is shown in Fig. 15. The two protein sequences show regions of high homology, confirming their phylogenic relationship. However, the region spanning amino acid 185 to 285 of the SENV-B sequence is highly divergent from its CWP SENV001 counterpart. In total, the two sequences share 55% of identity. Fig. 16 shows the alignment of the predicted amino acid sequence of the deduced ORF of SENV-B with ORF 1 of TTV. The two sequences show only 29% of identity. Furthermore, differences are uniformly scattered along the alignment of the two viral amino acid sequences. These data confirm that SENV-B is a subtype of SENV and that SENV and SENV-B sequences diverge significantly from the one of TTV. The low incidence of SENV in the healthy population contrasts sharply with the distribution of TTV in healthy groups. The data so far obtained suggest that SENV- or some of its subtypes may have important consequences for public health. Furthermore, other genetic variants of this viral agent, yet to be discovered, may vary in their ability to cause disease particularly, but not exclusively, of hepatic nature. EXAMPLE 8 Identification of additional 3 ' and 5' sequences of the SENV sequence In order to extend the CWP SEN001 (SEQ ID NO: 9) two different PCR reactions were performed. One reaction was performed with a 50-μl mixture containing template, 1/10 th of DNA extracted from 100 μl of serum from patient SEN with QIAamp blood kit (QIAGEN), PCR buffer (67 mM Tris HCI pH 8.8, 16.6 mM (NH 4 ) 2 S0 4 , 10mM β-mercaptoethanol, 2 mM MgCI 2 , 300ng of a single PCR primer), 200 μM deoxyribonucleoside triphosphates (dATP, dCTP, dTTP, dGTP from Boehringer, Mannheim, Germany), and 1.25 U of Taq polymerase (Perkin Elmer). The reaction was performed in a DNA thermal cycler with mineral oil. PCR consisted of a preheating at 94°C for 5 min, 45 cycles of 94°C for 1 min, 60°C for 1 min, and 72°C for 1 min, and an incubation at 72°C for 7 min. The primer used for this reaction was primer 8S (SEQ ID NO: 22) deduced from the 3' region of sequence CWP SEN001. The second reaction was performed with a 50-μl mixture containing template, 1/10 th of DNA extracted from 100 μl of serum from patient SEN with QIAamp blood kit (QIAGEN), PCR buffer (67 mM Tris HCI pH 8.8, 16.6 mM (NH 4 ) 2 S0 4 , 10mM β- mercaptoethanol, 2 mM MgCI≥), 300ng of a single PCR primer), 200 μM concentration of each deoxyribonucleoside triphosphate (Boehringer, Mannheim, Germany), and 1.25 U of Taq polymerase (Perkin Elmer). The reaction was performed in a DNA thermal cycler with mineral oil. PCR consisted of a preheating at 94°C for 5 min, 45 cycles of 94°C for 1 min, 60°C for 1 min, and 72°C for 1 min, and an incubation at 72°C for 7 min. The primer used for this reaction was primer 7AS (SEQ ID NO: 23) deduced from the 5' region of sequence CWP SEN001. In both cases, the PCR products were loaded on a 2% agarose gel with 2 μg of ethidium bromide per ml to determine the sizes of the amplified products. Gel slices corresponding to the 1200 and 1 100 bp bands, respectively, obtained with the two reactions were cut out. The DNA was extracted, cloned into a pGEM vector (Promega, Madison, WI, USA), introduced to E. Coli and sequenced. The DNA sequences of the inserts were determined using the AutoRead sequencing Kit (Pharmacia Biotech) with fluorescent M13 Universal primer and fluorescent M13 Reverse (Pharmacia Biotech). With this strategy two clones that overlapped the CWPSEN001 sequence both in 3' and in 5' were obtained. After assembling the overlapping sequences with the ASSEMLGEL program, a unique sequence of 3347 bases encoding for most of the SENV genome was obtained. This sequence was named SENV-A (SEQ ID NO: 24). Its translation in the 3 possible reading frames is shown in Fig. 17. The incompleteness of the sequence in the 5' region did not allow the verification of the presence of possible open reading frames in this region. However, an open reading frame of 676 amino acid ( SEQ ID NO: 25) starting from nucleotide 903 and ending to nucleotide 2831 was detected. At the nucleotide level, the SENV-A sequence shows an identity of 54% to the nucleotide sequence of TTV. Fig. 18 shows the alignment between these two sequences. The sequences are highly homologous at the 5' and at the 3' termini, however, they diverge substantially in the coding regions, showing that the two viruses are clearly distinct but belong to the same family. SEQ ID NO: 26 relates to the nucleotide sequence of SENV-A,. excluding the 5' and 3' portions which are highly homologous to TTV. The alignment of the nucleotide sequences encoding for the major ORF of SENV-A and TTV is shown in Figure 19. The identity between the two coding regions is only of 48% with the insertion of numerous gaps. The predicted proteins encoded by these two viruses (SENV-A and TTV) are even more divergent and share only 33% of identity (Fig. 20) showing that the two viruses are also serologically distinct. Interestingly, the ORF 1 of SENV-A contains at the C terminus of the sequence (position 617-638) the LQLVMFQLSRTQANLHLNPLSL leucine zipper pattern that is absent in the ORF 1 of TTV, suggesting that the two proteins may have different biological functions. This is also suggested by the absence in the SENV ORF of the high hydrophilic region characterized by an arginine rich domain present in the n- terminus of ORF1 of TTV. In addition to ORF1 the SENV-A sequence contains two other ORFs, ORF2 spans nucleotide 231 to 730 (SEQ ID NO: 28). This 166 amino acids sequence (SEQ ID NO: 27), rich in proline, was recognized in the first reading frame and its alignment with the ORF2 of TTV demonstrated that the two proteins have only 30% identity. ORF3, spanning nucleotides 2545 to 280/1 (SEQ ID NO: 30) overlaps with the 3' end of ORF1 but it was recognized on the first reading frame. The protein comprises only 87 amino acids (SEQ ID NO:29) but it contains an interesting nuclear binding region and a TATA motif was recognized 35 nucleotide upstream of the ATG starting codon, suggesting therefore that this potential reading frame is indeed translated. No equivalent ORF was detected in the TTV nucleotide sequence. EXAMPLE 9 Characterization of the SENV-B genome In order to obtain the complete sequence of the SENV-B genome two PCR reactions using primer SENVB0S (SEQ ID NO: 32), derived from the available sequence of SENV-B, and primer 10AS (SEQ ID NO: 33), derived from the most 3' region of the TTV sequence, and primers TTV 155 (SEQ ID NO: 72) and L 2AS (SEQ ID NO: 71) were set up. Since SENV and TTV share a common sequence in the 5' untranslated region of their genomes (see Fig. 18), it was likely that a region of sequence similarity would also exist in the most 3' region of the genomes. The PCR reaction were performed with a 50-μl mixture containing template, 1/10 th of DNA extracted from 100 μl of serum from patient NAE 8 with QIAamp blood kit (QIAGEN), PCR buffer (67 mM Tris HCI, pH 8.8, 16.6 mM (NH 4 ) 2 S0 4 , 10mM β-mercaptoethanol, 2 mM MgCI 2 ), 300ng of each PCR primer, a 200 μM concentration of each deoxyribonucleoside triphosphate (dATP, dGTP, dCTP, dTTP from Boehringer, Mannheim, Germany), and 1.25 U of Taq polymerase (Perkin Elmer). The reaction was performed in a DNA thermal cycler with mineral oil. PCR consisted of a preheating at 94°C for 5 min, 45 cycles of 94°C for 1 min, 60°C for 1 min, and 72°C for 1 min, and an incubation at 72°C for 7 min. As negative controls, the template was omitted from equivalent PCR reactions. The PCR products were loaded on a 2% agarose gel with 2 μg ethidium bromide per ml in order to determine the size of the amplified products. Using this strategy an amplicon of about 1400 bp was obtained. Gel slices corresponding to a 1400 bp and a 1200 bp band which were obtained by PCR were cut out, and the purified DNA extract was connected to a pGEM vector according to standard and manufacturers' protocols (Promega, Madison, WI, USA) and introduced into E. coli. The DNA sequences of the inserts were determined by using the AutoRead sequencing Kit (Pharmacia Biotech) with fluorescent M13 Universal primer and fluorescent M13 Reverse. Sequences were determined on three clones of the respective PCR products, and the consensus sequence was adopted. Using this strategy, several clones that overlapped the 3' and the 5' regions of the available SENV-B sequence (SEQ ID NO: 20) were obtained. After assembling the overlapping sequences with the ASSEMLGEL program, PC GENE software system (University of Geneva, Switzerland; ™ IntelliGenetics Inc.) a unique sequence of 3619 bases was obtained. This sequence was named SENV-B (SEQ ID NO: 34). As SENV-A, SENV-B contains three open reading frames. The first one, ORF 2 (SEQ ID NO: 35), starts from nucleotide 259 and ends at nucleotide 727, the second one, ORF1 (SEQ ID NO: 36), starts at nucleotide 831 and ends at nucleotide 2870, while, another open reading frame (ORF3) (SEQ ID NO: 37), spans nucleotide 2598 to 2847. At the nucleotide level, the SENV-B sequence shares 68.12% of identity to the nucleotide sequence of SENV-A. Figure 22 shows the alignment of these two sequences. Interestingly, the sequences are highly homologous at the 5' and the 3' termini while they diverge in the coding regions. The alignment of the amino acid sequences encoding for the major ORF (ORF1) of SENV-A and full-length ORF1 of SENV-B and of TTV ORF1 are shown in Figures 23 and 24, respectively. The identity between the SENV-A and SENV-B ORF1 is 56.07%, while the ORF1 of TTV shares only 34.76 % of identity with the corresponding full-length ORF of SENV-B. These data strongly suggest that TTV and SENV are different viruses and that SENV-B is a genotype of SENV-A. Figures 25 and 26 show the alignment of the ORF 2 and ORF3 sequences of SENV-A and SENV-B. The identity between the two ORF2 is 33.33%, while the one between the two ORF3 is 27.71%, indicating that these proteins are specific subtypes and confer genotype different tropism or different biological functions to these SENV subtypes. Furthermore, SENV-B ORF2 shares 22.84% amino acid identity with TTV ORF2. The nucleotide sequences encoding the SENV-B ORF1 , ORF2 and ORF3 are shown in SEQ ID NO: 38, SEQ ID NO: 39 and SEQ ID NO: 40, respectively. The alignment of the nucleotide sequences of SENV-A and SENV- B ORF1 and ORF2 regions are shown in Figures 27 and 28. The two ORF1 of SENV-A and SENV-B share 63.40% of identity, while the ORF2 of both SENV subtypes share a nucleotide identity of 49,68%. Figures 29 and 30 show the nucleotide alignment of the SENV-B ORF1 and ORF2 sequences, respectively, with the corresponding region of TTV. The two ORF1 sequences share only 49.85% of identity, and the best alignment requires the insertion of numerous gaps. The ORF2 segments of the two viral agents, TTV and SENV-B, have a even lower identity (41.83%). Therefore, SENV-B can be considered as being a subtype of SENV-A, and both SENV subtypes are only distantly related to TTV. EXAMPLE 10 Identification of four major SENV genotypes Having established that SENV has at least two different subtypes, two primers, L1S (SEQ ID NO: 41) and L3AS primers (SEQ ID NO: 42), were designed that are potentially suitable for amplifying both subtypes in the same PCR reaction. The primers were designed on the basis of the alignment between SENV-A and SENV-B ORF1 sequences and on the basis of their nucleotide composition which made them the best candidates for amplifying conserved regions of the two SENV subtypes. In order to establish the analytical performance of these primers, PCR reactions using DNA extracted from the sera of 6 non-A non-E hepatitis patients (NAE) were set up. The PCR reactions were performed with a 50-μl mixture containing template, 1/10 th of DNA extracted from 100 μl of serum from NAE patients with QIAamp blood kit (QIAGEN), PCR buffer (67 mM Tris HCI, pH 8.8, 16.6 mM (NH 4 ) 2 S0 4 , 10mM β- mercaptoethanol, 2 mM MgCI 2 ), 300ng of each PCR primer, a 200 μM concentration of each deoxyribonucleoside triphosphate (dATP, dGTP, dCTP, dTTP from Boehringer, Mannheim, Germany), and 1.25 U of Taq polymerase (Perkin Elmer). The reaction was performed in a DNA thermal cycler with mineral oil. PCR consisted of a preheating at 94°C for 5 min, 45 cycles of 94°C for 1 min, 55°C for 1 min, and 72°C for 1 min, and an incubation at 72°C for 7 min. In negative controls, the template for PCR reactions was omitted. On 2% agarose gels, the obtained PCR products from all 6 patient samples migrated as a band of the expected size (450 bp), although small differences in the band sizes were detectable. In order to verify the specificity of the PCR products gel slices, corresponding to the 450 bp bands obtained by the PCR reactions, were cut out, the extracted DNA was connected to a pGEM vector (Promega, Madison, WI, USA) and the vector was introduced into E. coli. The DNA sequences of the inserts were determined by using the AutoRead sequencing Kit (Pharmacia Biotech) with fluorescent M13 Universal primer and fluorescent M13 Reverse. By this approach, 14 nucleotide sequences of SENV ORF1 (SEQ ID NO: 43-56) could be obtained. The alignment of the translated product of these sequences (SEQ ID NO: 57-70) is shown in Fig. 31. Fig. 31 also depicts the sequences of the corresponding region of SENV-A (encoded by nucleotides 1372-1830 of SEQ ID NO: 24) and SENV-B (encoded by nucleotides 1379-1879 of SEQ ID NO: 34). The evolutionary relationship between different viruses can be established by calculating the phylogenic distances between aligned nucleotide or aligned deduced amino acid sequences of their large open reading frames or of portions of these sequences. In order to determine the phylogenetic relationship between the different SENV sequences, as shown in Fig. 31 , evolutionary distances were determined by alignments of nucleotide sequences of the analyzed segment of ORF1 (Fig. 31). Besides SENV-A and SENV-B sequences, the most homologous TTV sequences and homologous sequences of an unrelated virus (HGV) were included in the analysis. The relative evolutionary distances between the viral sequences analyzed were readily apparent upon inspection of the unrooted phylogenetic trees (see Fig. 32). Phylogenetic distances were estimated employing the PROTDIST program of the PHYLIP package. These calculated distances were used for the construction of phylogenetic trees using the program NEIGHBOR (neighbor-joining setting). The program DRAWTREE produced the final representation. All the programs were obtained from the www. Net. This phylogenetic analysis suggests upon visual inspection the existence of four major SENV subtypes: SENV-A comprising the sequence encoded by nucleotides 1372-1830 of SEQ ID NO: 24, SENV-B comprising the sequence encoded by nucleotides 1379-1879 of SEQ ID NO: 34 as well as SEQ ID NO: 55 and 56, SENV-C comprising SEQ ID NO: 43-50 and SENV-D comprising SEQ ID NO: 51-54. In addition, the unrooted tree graphically demonstrates the significant degree of divergence of the SENV genotypes from TTV. EXAMPLE 11 Characterization of SENV-C genome In order to obtain the complete sequence of the SENV-C genome two PCR reactions were set up, to extend the obtained sequence in 3' and 5' direction. In one reaction, primers L2AS ( SEQ ID NO: 71 ), derived from the available sequence of SENV-C (SEQ ID NO: 45), and TTV15S (SEQ ID NO: 72), derived from the most 5' region of the TTV sequence, were used. In the second reaction, primer SEN-C1S (SEQ ID NO: 73), derived from the available sequence of SENV-C (SEQ ID NO: 45), and primer 66AS (SEQ ID NO: 74), derived from the 3' sequence of SENV-A, were employed. Since SENV-A and SENV-B share a common sequence in the 3' untranslated region of their genomes, it was expected that a similar region of sequence similarity would exist in the most 3' region of the genomes of SENV-C. The PCR reactions were performed with a 50-μl mixture containing template, 1/10 th of DNA extracted from 100 μl of serum from patient NAE 8 with QIAamp blood kit (QIAGEN), PCR buffer (67 mM Tris HCI, pH 8.8, 16.6 mM (NH 4 ) 2 S0 4 , 10mM β- mercaptoethanol, 2 mM MgCI 2 ), 300ng of each PCR primer, a 200 μM concentration of each deoxyribonucleoside triphosphate (dATP, dGTP, dCTP, dTTP from Boehringer, Mannheim, Germany), and 1.25 U of Taq polymerase (Perkin Elmer). The reaction was performed in a DNA thermal cycler with mineral oil. PCR consisted of a preheating at 94°C for 5 min, 45 cycles of 94°C for 1 min, 60°C for 1 min, and 72°C for 1 min, and an incubation at 72°C for 7 min. Using this strategy two amplicons of about 1400 bp and 1500 bp were obtained. The PCR products were loaded on a 2% agarose gel with 2μg ethidium bromide per ml in order to determine the size of the amplified products. Gel slices corresponding to these 1400 bp and 1500 bp bands were cut out, the DNA extracts were connected to a pGEM vector (Promega, Madison, WI, USA), and the vector was introduced into E. coli. The DNA sequences of the inserts were determined using the AutoRead sequencing Kit (Pharmacia Biotech) with fluorescent M13 Universal primer and fluorescent M13 Reverse. Again, three clones were sequenced (both strands), and the consensus sequence was adopted. By using this strategy several clones that overlapped the 5' and 3' regions of the available SENV-C sequence (SEQ ID NO: 43-50) were obtained. After assembling the overlapping sequences with the ASSEMLGEL program, a unique sequence of 3313 bases was obtained. This sequence was named SENV-C (SEQ ID NO: 75). As SENV-A and SENV-B, this SENV-C sequence contains three open reading frames, but an additional ORF was also detected. The nucleotide sequences of ORF1 (nt 579-2840), 2 (nt 232-705) , 3 (nt 2548-2814) and 4 (nt 2588-2944) (SEQ ID NO: 76- 79) encode for proteins of 753, 157, 88, and 118 amino acids (SEQ ID NO: 80-83), respectively. The alignment of the amino acid sequences encoding for the major ORF (ORF1 ) of SENV-C with ORF1 of SENV-A, SENV-B and of TTV is shown in Figures 33, 34 and 35, respectively. The identities between the SENV-C ORF1 with the ORF1 of SENV- A and SENV-B are 51.56% and 50.37%, respectively, while the identity between SENV-C ORF1 and TTV ORF1 is 34.93%. The alignment of the amino acid sequences encoding for the ORF2 of SENV-C with ORF2 of SENV-A, SENV-B and of TTV is shown in Figures 36, 37 and 38, respectively. The identities between the SENV-C ORF2 with the ORF2 of SENV-A and SENV-B are 46.50% and 34.62%, respectively, while the identity between SENV-C ORF2 and TTV ORF2 is 35.67%. Finally, a comparison of the ORF3 of SENV-C with the ORF3 of SENV-A and SENV- B is shown in Figures 39 and 40, respectively. The percentage of identity between SENV-C ORF3 and SENV-A ORF3 and SENV-B ORF3 is 47.67% and 36.14%, respectively. The full-length SENV-C nucleotide sequence shares 67.76% and 66.71% of identity to the nucleotide sequence of SENV-A and SENV-B, respectively. The alignment of the nucleotide sequences encoding for the major ORF1 of SENV-C with ORF1 of SENV-A, SENV-B and of TTV is shown in Figures 41 , 42 and 43, respectively. The identities between the SENV-C ORF1 with the ORF1 of SENV-A and SENV-B are 65.63% and 63.92%, respectively, while the identity between SENV-C ORF1 and TTV ORF1 is 48.52%. The alignment of the nucleotide sequences encoding for the ORF2 of SENV-C with the one of SENV-A, SENV-B and of TTV are shown in Figures 44, 45, and 46, respectively. The identities between the SENV-C ORF2 with the ORF2 of SENV-A and SENV-B are 63.27% and 60.93%, respectively, while the identity between SENV-C ORF2 and TTV ORF2 is 52.02%. Finally, a comparison of the nucleotide sequence ORF3 of SENV-C with the nucleotide sequence ORF3 of SENV-A and SENV-B is shown in Figures 47 and 48, respectively. The percentage of identity between SENV-C ORF3 and SENV-A ORF3 and SENV-B ORF3 is 65.50% and 62.70%, respectively. EXAMPLE 12 Characterization of SENV-D genome In order to obtain the complete sequence of the SENV-D genome two PCR reactions were set up in order to obtain 3' and 5' extended sequences. In one PCR reaction primers SENV-D 2AS (SEQ ID NO: 84) and TTV15S (SEQ ID NO: 72), derived from the available sequence of SENV-D (SEQ ID NO: 53) and from the most 5' region of the TTV sequence, were used. In the second reaction, primer SENV-D 1S (SEQ ID NO: 85), derived from the available sequence of SENV-D (SEQ ID NO: 53), and primer 662AS (SEQ ID NO: 86), derived from the 3' sequence of SENV-C, were utilized. The PCR reactions were performed with a 50-μl mixture containing template, 1/10 th of DNA extracted from 100 μl of serum from patient NAE 8 with QIAamp blood kit (QIAGEN), PCR buffer (67 mM Tris HCI, pH 8.8, 16.6 mM (NH 4 ) 2 S0 4 , 10mM β- mercaptoethanol, 2 mM MgCI 2 ), 300ng of each PCR primer, a 200 μM concentration of each deoxyribonucleoside triphosphate (dATP, dGTP, dCTP, dTTP from Boehringer, Mannheim, Germany), and 1.25 U of Taq polymerase (Perkin Elmer). The reaction was performed in a DNA thermal cycler with mineral oil. PCR consisted of a preheating at 94°C for 5 min, 45 cycles of 94°C for 1 min, 58°C for 1 min, and 72°C for 1 min, and an incubation at 72°C for 7 min. Using this strategy two amplicons of about 1350 bp and 1614 bp were obtained. The PCR products were loaded on a 2% agarose gel with 2μg ethidium bromide per ml in order to determine the size of the amplified products. Gel slices corresponding to said 1350 bp and 1914 bp bands were cut out, the DNA extracts were connected to a pGEM vector (Promega, Madison, WI, USA), and the vector was introduced into E. coli. The DNA sequences of the inserts were determined by using the AutoRead sequencing Kit (Pharmacia Biotech Sweden) with fluorescent M13 Universal primer and fluorescent M13 Reverse. Three clones were sequenced (both strands), and the consensus sequence was adopted. Several clones that overlapped the 5' and 3' regions of the available SENV-D sequence (SEQ ID NO: 51-54) were obtained. After assembling the overlapping sequences with the ASSEMLGEL program a unique sequence of 3264 bases was deduced. This sequence was named SENV-D (SEQ ID NO: 87). SENV-D contains three open reading frames. The nucleotide sequences of ORF1 (nt 584-2848), ORF2 (nt 252-725) and ORF3 (nt 2550-2816) (SEQ ID NO: 88, 89 and 90) encode for proteins of 754, 157 and 88 amino acids (SEQ ID NOs: 91 , 92 and 93), respectively . At the nucleotide level, the ORF1 SENV-D sequence shares 64.39%, 58.73% and 60.43% of identity to the ORF1 nucleotide sequence of SENV-A, SENV-B and SENV-C respectively. The identity of the SENV-D ORF1 nucleotide sequence with the nucleotide sequence encoding for TTV ORF1 is 49.01 %. The alignment of the nucleotide sequences encoding SENV-D ORF2 with the nucleotide sequence encoding ORF2 from SENV-A, SENV-B, SENV-C or TTV demonstrates that these sequences share 57.59%, 57.32%, 52.11 % and 47.47 %, respectively, of identity. The alignment of the nucleotide sequences encoding SENV-D ORF3 with the nucleotide sequence encoding ORFs3 from SENV-A, SENV-B and SENV-C demonstrated that these sequences share 55.81 %, 55.95% and 57.68%, respectively, of identity. Furthermore, the alignment of the amino acid sequences of ORF1 of SENV-D with the ORF1 of SENV-A, SENV-B, SENV-C and of TTV demonstrates that these protein sequences share 56.07%, 49.48%, 52.32% and 34.62%, respectively, of identity (see Figure 50A). The alignment of the amino acid sequences of ORF2 of SENV-D with the ORF2 of SENV-A, SENV-B, SENV-C and of TTV demonstrates that these sequences share 40.13%, 45.51%, 34.39% and 20.38%, respectively, of identity (see Figure 50B). Finally, a comparison of the ORF3 of SENV-D with the ORF3 of SENV-A and SENV- B and SENV-C demonstrates that these sequences share 38.37%, 31.33% and 29.55%, respectively, of identity (see also Figure 50C). EXAMPLE 13 Comparative analysis of SENV sequences Figure 49A summarizes the percentage of nucleotide identities between the whole genomes (Figure 49A) or the sequence encoding the different ORFs (Figure 49C, 49D and 49E) of SENV-A, SENV-B, SENV-C, SENV-D and the genome of TTV. The same analysis (Figure 49B) was also carried out considering only the complete coding regions of SENV (SEQ ID NO:s 26, 94, 95 and 96). Thus, even considering the conserved 5' and 3' untranslated regions between SENV and TTV, the nucleotide sequences of these two viral agents never share more than 60% of identity. Figure 50 summarizes the percentage of identities at the amino acid levels of the ORFs encoded by SENV-A, SENV-B, SENV-C, SENV-D and TTV genomes. It is of note that the amino acid sequence identities of all deduced SENV ORFsl with ORF1 of TTV lay in the same range (between 33.18% and 34.93%), whereas the ORF1 identities among the SENV subtypes are in a much higher range (49.48% to 56.07%). This suggests that the SENV has evolved independently from TTV and that the phylogenic separation between TTV and SENV ancestor has occurred before the evolution of the different SENV genotypes. Furthermore, SENV ORFs2 and ORFs3 are much less conserved than SENV ORFsl . In order to better evaluate the relationship among the different SENV sequences, an evolutionary analysis of the ORF1 and ORF2 amino acid sequences was carried out. The evolutionary relationship among different viruses can be examined by calculating the phylogenic distances between aligned nucleotide or aligned deduced amino acid sequences of large open reading frames or of a portion of these sequences. In order to determine the phylogenetic relationship between the different SENV sequences, evolutionary distances were determined for alignments of amino acid sequences of ORF1 and ORF2. Figure 51 shows the results of this analysis. The relative evolutionary distances between the viral sequences analyzed are readily apparent from the numeric values. Concerning ORFsl , Fig. 52 shows also the unrooted phylogenic tree derived from alignments of the amino acid sequences. Essentially this analysis shows that, at least for ORF1 , all SENV sequences are more related to each other than to TTV and that, as already deduced by the analysis of the percentage of identities, all SENV sequences have the same phylogenic distance from TTV. In conclusion all these data establish that SENV and TTV are different viruses that probably evolved from a common ancestor. EXAMPLE 14 Detection of SEN viruses in clinical studies The cumulative prevalence of SEN-viruses in different groups of clinically informative individuals was evaluated. To this end a PCR strategy capable of amplifying simultaneously SENV-A, SENV-B, SENV-C and SENV-D sequences was developed. For this PCR, primers BCD 1 S ( SEQ ID NO: 97) and L 2AS (SEQ ID NO: 71) were used which were derived from conserved sequences among SENV-A, SENV-B, SENV-C and SENV-D. The PCR reactions were performed with a 50-μl mixture containing template, 1/10 th of DNA extracted from 100 μl of serum with QIAamp blood kit (QIAGEN), PCR buffer (67 mM Tris HCI, pH 8.8, 16.6 mM (NH 4 ) 2 S0 4 , 10mM β-mercaptoethanol, 2 mM MgCI 2 ), 300ng of each PCR primer, a 200 μM concentration of each deoxyribonucleoside triphosphate (dATP, dGTP, dCTP, dTTP from Boehringer, Mannheim, Germany), and 1.25 U of Taq polymerase (Perkin Elmer). The reaction was performed in a DNA thermal cycler with mineral oil. PCR consisted of a preheating at 94°C for 5 min, 40 cycles of 94°C for 1 min, 54°C for 1 min, and 72°C for 1 min, and an incubation at 72°C for 7 min. PCR products were analyzed on 2% agarose gels. In order to evaluate the specificity of the amplified products, aliquots of 5 μl of each amplified product were hybridized in a DEIA assay (DNA Enzyme Immunoassay; Mantero, Chemical Chemistry 37 (1991 ), 422-429) with the following biotinylated probes: a SEN probe (SEQ ID NO: 98), specific for a conserved sequence in the middle within the amplified DNA, LA (SEQ ID NO: 99), specific for SENV-A sequences, LB (SEQ ID NO: 100), specific for SENV-B sequences, LC (SEQ ID NO: 101 ), specific for SENV-C sequences LD (SEQ ID NO: 102) specific for SENV-D sequences. Thus, each amplified product could be simultaneously tested for the presence of total SENV sequences as well as for each specific genotype/subtype. By using this method, sera from different groups of individuals were analyzed and the results are shown in Fig. 53. It can be established that SENV had a low prevalence among blood donors, while it was surprisingly found that the majority of patients with advanced liver disease of unknown origin were positive for this (these) viral agent(s). Furthermore, the high prevalence of SEN virus among intravenous drug users also suggests that the virus can be transmitted with blood. EXAMPLE 15 Molecular organization of SEN viruses In order to further understand the relationship between the different SEN, the presence of biologically significant sites and signatures in the different hypothetical proteins encoded by the genomes of the viruses were analyzed. According to PROSITE prediction (PC GENE software system (University of Geneva, Switzerland; ™ IntelliGenetics Inc.)), the ORFsl of SENV-A, B, C and D contain 2, 1 , 1 and 1 potential N-glycosylation sites, 1 , 1 , 4 and 1 tyrosine sulfatation sites, 6, 11 , 9 and 10 proteinkinase C-phosphorylation sites, 9, 5, 9 and 6 caseinkinase II- phosphorylation sites, 2, 1 , 4 and 3 amidation sites and 2, 5, 4 and 5 N-myristoylation sites, respectively. SENV-A and SENV-C ORFsl were also characterized by the presence of a leucine pattern spanning positions 617-638 and 729-750, respectively. Furthermore, SENV-C ORF1 also contained a microbodies C-terminal signal spanning position 751-753. Finally SENV-C and SENV-D contained 20 and 21 bipartite nuclear targeting sequences at the N-termini. None of these sequences were found in SENV-A and SENV-B ORFsl . The same type of analysis was applied to ORF2 and revealed that the SENV-A, B, C and D ORFs2 contain 0, 0, 0 and 1 potential N-glycosylation sites, 0, 1 , 1 and 0 tyrosine sulfatation sites, 1 , 0, 0 and 2 proteinkinase C-phosphorylation sites, 1, 1 , 0 and 1 caseinkinase ll-phosphorylation sites, and 1 , 6, 7 and 3 N-myristoylation sites, respectively. SENV-A and SENV-C ORFsl were also characterized by the presence of a leucine pattern spanning positions 617-638 and 729-750, respectively, which cannot be detected in ORF1 of TTV. ORFs3 of SENV-A, B, C and D were characterized by the presence of 1 , 4, 3 and 0 cAMP and cGMP-dependent proteinkinase phosphorylation sites, 1 , 4, 6 and 4 proteinkinase C-phosphorylation sites, 2, 2 1 and 3 caseinkinase il-phosphorylation sites, 1 , 0, 1 and 1 amidation sites and by 2, 2, 4 and 4 bipartite nuclear targeting sequences, respectively. Example 16 Cloning and expression of recombinant SENV-A proteins The ORF1 of SENV-A cloned into the EcoRl restriction site of ρGEM * -T Easy (Promega) was amplified by PCR in order to add at the 5' and the 3' termini two restriction site sequences. The upper primer has a non-complementary BamHI recognition sequence at the 5' end: TTG GAT CCA TGA ACT ATG CCA TGC ACT GCG (SEQ ID NO: 109), whilst the lower primer has an EcoRl recognition sequence at the 5' end: ATG AAT TCT TAC GTG AGG TGT GCT AAA GAT AGT GGG (SEQ ID NO: 110). The amplicon obtained was cloned into pET-30a E. coli expression vector (Novagen) in order to express the ORF1 as a fusion protein with an histidine tail at the N-terminus. This tail allows an easier purification onto a metal chelating column (HI TRAP Chelating Pharmacia, # 17-0409-01 , used according to manufacturer's protocols). The induction protocol of transformed E. coli BL21 strain was performed according to the pET system manual (Novagen): briefly, an overnight culture of recombinant E. coli was inoculated at a dilution of 1 :50 in fresh medium. The cells were incubated on a shaker at 37°C until the culture reached an optical density of OD600 0.5-0.6. The cells were then induced adding IPTG from a 100mM stock to a final concentration of 1 mM. In a time course experiment it was determined that, regardless of the time of induction, the level of expression of target protein expression after induction remained quite low. Therefore, an induction time of three hours was set for the recombinant ORF1 in order to obtain a protein sample which could be purified and used for preliminary immunoreactivity analysis. In order to evaluate the solubility of the expressed protein, an extraction protocol comprising three steps was carried out: first, the cellular pellet is resuspended in a Tris buffer (50mM Tris-HCl, 100 mM NaCl pH 8.0) and sonicated. After a centrifugation step, the pellet is resuspended in a urea buffer (8M Urea, 50 mM Tris-HCl, 100 mM NaCl pH 8.0) and heated at 70°C to recover the insoluble protein fraction. The residual pellet (if present) is resuspended into SDS-PAGE loading buffer. The majority of recombinant ORF1 protein is found in the urea fraction and was purified by affinity chromatoghaphy on a metal chelation resin. A partially purified fusion protein of 80354 dalton of molecular weight was obtained (see table # 1 ; SEQ ID NO: 103 and SEQ ID NO: 104). TABLE 1 Recombinant ORF1 A Nucleotide sequence: ATGCACCATCATCATCATCATTCTTCTGGTCTGGTGCCACGCGGTTCTGGTAT GAAAGAAACCGCTGCTGCTAAATTCGAACGCCAGCACATGGACAGCCCAGAT CTGGGTACCGACGACGACGACAAGGCCATGGCTGATATCGGATCCATGAAC TATGCCATGCACTGCGAAGACAGCACCCCGCAGCCAGAACCTTTCGGGGGC GACATGTCCACAATAACTTTCAGCCTGCTGGTACTATACGACCAGCACGAGA GACACCTTAACAGGTGGACGTTCCCCAACGACCAGCTAGACCTGGTGAGGT ACAAACACACCAGGTTTAAATTTTACAGAAGCAAAGACACTGACTTTATAGTT ACCTTTAACATAAAGCCTCCCATGAAAATGAACGAGACTACCTCACCGAACG CGCACCCGGGCATGCTAATGCAGATGAAACACAAAATACTCGTGCCCAGCTT TCAAACTAGACCCGGGGGGCGCAGATACGTGTCTGTAAAGATAGGGCCCCC CAAACTGTTTGAAGACAAGTGGTACCCACAGGCAGACTTTTGCAAGGTTCCC CTTGTCAGTTTAACCGCAACCGCAGCTGACTTCAGACATCCGTTCTGCTCAC CACAAACGAACAACCCTTGCACCACCTTCCAGGTGTTGCGAGAACAGTACAA CAAAGTAATAGGCTTCCCCATGAAAGGGGAAGAGGCCTACACTGACTTTGAA AACTGGCTATATGAGTCTGGGGGCCACTATCAGACCTTTCAAACCGAGGCTC AATTTAGAGTTCCCTTACATAAACCCGATGGTGACACAAATAACAAAAAAGAG GACTGGACAAACATGTGGTCAGGTACGAATGGCATATACCACAAAAAGGCAG ACAGTAACTATGGCTATCACTCCTTTCAAGTTAAAGGTAAAAAAAAGAACATA ACAAAAAGAAGAGACATTCAATTTGAATGGGAAACTAAATTCACTGAACAAGC AACACACATAAACCCCACATGGCAACCGGGCCACTTTAAACAGTACGAATAT CACCTGGGCTGGTTCAGTCCCATATTCATAGGCCCCAACAGATACAACACCC AGTTTCGCCCCGCATACTATGATGTTACCTACAACCCCTTTAATGACAAGGGC AAAGGTAACATAATCTGGTTTCAGTACCTAACAAAACCAGACACAGAGTTCGA CCCCCTTCAGTGCAAGTGTGTCATTGAAGACATCCCACTGTGGGCGGCCTTC TTTGGCTACCCAGACTACATAGAGAGCCAGCTAGGCCCCTTCCAAGACCACG AGACAGTAGGCATAGTGTGTTTCATATGCCCATACACAGTTCCCCCCATGTA CAAACCAGGCAAGCAACAAATGGGCTACGTATTCTATGACACTAACTTTGGA AACGGAAAGATGCCCTCCGGACTGGGACAGATACCCGTATACTGGCAGAGC AGGTGGCGACCGTACCTAAAATGGCAGCTACAAGTAATGAATGACATTTGCA AGACGGGACCGTTTTCATACAGAGACGAACTGAAGCAGGCGCAGCTGTGTG CCATGTACAGTTTTAAATTCCTATTTGGGGGCGACTTACTGTATCCACAGATC ATTAAAAACCCCTGTGGAGACTCCGGAGTGCCCTCCAGTCCCGGTAGACAG CCTCGCAGCGTACAAGTCACGAACCCGCTCTCCATGGCCCCCCAGTTCATCT TCCACAAATTTGACACCAGACGTGGGTTCTATAGCTCAGCTTCTCTCAAAAGA ATGCTTCAAAAACCAACAGATGATGAACTCTATCTTAAAAAACCAAAATTCCC TCGCTTGCTTACAGCCCTACAAGGAGACCAAGGGCAAGAAGACAGCTTCAGT TCACAGGAAGCAAGCGAGCAGTCCTCGCAAGAGGAGAAAGAAGCAGAAGCC CCCCAAACGCAAGCGCAGATACAGCAGCAGCTCAGACAGCAGCTCAAACAG CAGGTCCAACTCCGAAACCAGCTGCAGCTCGTCATGTTCCAACTCTCCCGCA CGCAAGCCAATTTACATTTAAACCCACTATCTTTAGCACACCTCACGTAA Bold: The 1 st ATG of the sequence ORF1 protein sequence: MHHHHHHSSGLVPRGSGMKETAAAKFERQHMDSPDLGTDDDDKAMADIGSMNYA MHCEDSTPQPEPFGGDMSTITFSLLVLYDQHERHLNRWTFPNDQLDLVRYKHTRF KFYRSKDTDFIVTFNIKPPMKMNETTSPNAHPGMLMQMKHKILVPSFQTRPGGRRY VSVKIGPPKLFEDKWYPQADFCKVPLVSLTATAADFRHPFCSPQTNNPCTTFQVLR EQYNKVIGFPMKGEEAYTDFENWLYESGGHYQTFQTEAQFRVPLHKPDGDTNNKK EDWTNMWSGTNGIYHKKADSNYGYHSFQVKGKKKNITKRRDIQFEWETKFTEQAT HINPTWQPGHFKQYEYHLGWFSPIFIGPNRYNTQFRPAYYDVTYNPFNDKGKGNII WFQYLTKPDTEFDPLQCKCVIEDIPLWAAFFGYPDYIESQLGPFQDHETVGIVCFICP YTVPPMYKPGKQQMGYVFYDTNFGNGKMPSGLGQIPVYWQSRWRPYLKWQLQV MNDICKTGPFSYRDELKQAQLCAMYSFKFLFGGDLLYPQIIKNPCGDSGVPSSPGR QPRSVQVTNPLSMAPQFIFHKFDTRRGFYSSASLKRMLQKPTDDELYLKKPKFPRL LTALQGDQGQEDSFSSQEASEQSSQEEKEAEAPQTQAQIQQQLRQQLKQQVQLR NQLQLVMFQLSRTQANLHLNPLSLAHLT Underlined: histidine tail and S:Tag sequence Bold: 1 st methionine of the ORF1 sequence The ORF2 of SENV-A cloned into the EcoRl site of pGEM * -T Easy vector (Promega) was PCR amplified in order to insert two restriction site recognition sequences at the 5' and 3' end of the sequence. The forward primer has a BamHI site at the 5' end: ATG GAT CCG GGC TAT GGG CAA GGC TCT TAG GG (SEQ ID NO: 1 1 1 ); the reverse primer has an EcoRl recognition sequence at the 5' end: TAG AAT TCT TAC TGT TGG TCG TCT TCT TCG ACG G (SEQ ID NO: 1 12). The sequence obtained was cloned into pET30c E. coli expression vector (Novagen) and expressed as a fusion protein with an histidine tail at the N-terminus. After a time course study of target protein expression, a three hours induction time was set. The same extraction as for the recombinant ORF1 of SENV-A was employed. The recombinant ORF2 of SENV-A was recovered into the urea fraction. The fusion protein, purified on a metal chelating column (see above), has a molecular weight of 24000 dalton (see table # 2; SEQ ID NO: 105 and SEQ ID NO: 106) TABLE 2 Recombinant ORF2 A Nucleotide sequence ATGCACCATCATCATCATCATTCTTCTGGTCTGGTGCCACGCGGTTCTGGTAT GAAAGAAACCGCTGCTGCTAAATTCGAACGCCAGCACATGGACAGCCCAGAT CTGGGTACCGACGACGACGACAAGGCCATGGGATATCTGTGGATCCGGGCT ATGGGCAAGGCTCTTAGGGTTATCGCTCTTAAAATGCCCTTTCTCGGCAGGG TCTGGAGAAAGAAAAGGAAAGTGCTTCTGCAAGCTGTGCCAACTACACAGAC TACACCTGCCATGAGCTGGTTCCCCCCAGTGCATAATGCCGCCGGCAGAGA AAGAAATTACTGGGAATGCTGCTTTAGGGCGCACGCATGTTTTTGTGGTTGT GGCAATTTCATTCGCCACCTTAATCTTCTAGCTAATCATTATCACTTCGACCCG CCGGCACCTCCGCCCAATAATCCCCCACCGGGGCCAAAACCAACACTGAGGG CCCTGCCTCCCGTTCCCGGCGACCCGGCGGACCCTCCTAACCCAGGCCCGCA ATGGCCTGGGGCTAATGACAACACAAACACTAGGGCACCCACCGCTGGCGAA GGAGAAAGAGGCGCCGCCGACCACTATGAAGACGCCGAGCTCAACGCCCTCT TCGCCGCCGTCGAAGAAGACGACCAACAGTAA Bold: 1 st ATG of the ORF2 ORF2 protein sequence: MHHHHHHSSGLVPRGSGMKETAAAKFERQHMDSPDLGTDDDDKAMGYLWIRA MGKALRVIALKMPFLGRVWRKKRKVLLQAVPTTQTTPAMSWFPPVHNAAGRER NYWECCFRAHACFCGCGNFIRHLNLLANHYHFDPPAPPPNNPPPGPKPTLRAL PPVPGDPADPPNPGPQWPGANDNTNTRAPTAGEGERGAADHYEDAELNALFA AVEEDDQQ Underlined: Histidine tail and S.Tag sequence Bold:1 st methionine of ORF2 The ORF3 of SENV-A was excised from the EcoRl site of a recombinant pGEM * -T Easy vector and amplified by PCR in order to add two unique restriction site recognition sequences at the 5' and 3' termini. The forward primer used has a BamHI recognition sequence at the 5' end: ATG GAT CCC CAA CAG TAG ATG AAC TCT ATC TTC AAA AAC C (SEQ ID NO: 113), the reverse primer has an EcoRl binding sequence at the 5' end: TAG AAT TCT GGA ACA TGT CAT ACT TTA CGT GAG GTG TGC (SEQ ID NO: 114). The amplified product was cloned into the pET30b E.coli expression vector and, after 3 hours of induction, the bacteria have been harvested. The protein extraction protocol was the same as for the ORF1 and the recombinant protein was found in the soluble Tris fraction. The recombinant protein, purified on a metal chelating column, has a molecular weight of 15000 dalton (see table # 3; SEQ ID NO: 107 and SEQ ID NO: 108). TABLE 3 Recombinant ORF3 A Nucleotide sequence: ATGCACCATCATCATCATCATTCTTCTGGTCTGGTGCCACGCGGTTCTGGTAT GAAAGAAACCGCTGCTGCTAAATTCGAACGCCAGCACATGGACAGCCCAGAT CTGGGTACCGACGACGACGACAAGGCCATGGCGATATCGGATCCCCAACAG ATGATGAACTCTATCTTCAAAAACCAAAATTCCCTCGCTTGCTTACAGCCCTA CAAGGAGACCAAGGGCAAGAAGACAGCTTCAGTTCACAGGAAGCAAGCGAG CAGTCCTCGCAAGAAGAGAAAGAAGCAGAAGCCCCCCAAACGCAAGCGCAG ATACAGCAGCAGCTCAGACAGCAGCTCAAACAGCAGGTCCAACTCCGAAAC CAGCTGCAGCTCGTCATGTTCCAACTCTCCCGCACGCAAGCCAATTTACATTTA A Bold: 1 st ATG of the ORF3 ORF3 protein sequence: MHHHHHHSSGLVPRGSGMKETAAAKFERQHMDSPDLGTDDDDKAMAISDPQQM MNSIFKNQNSLACLQPYKETKGKKTASVHRKQASSPRKKRKKQKPPKRKRRYSSS SDSSSNSRSNSETSCSSSCSNSPARKPIYI Underlined: histidine tail and S-Tag sequence Bold: 1 st methionine of ORF3 Example 17 Detection of SEN viruses in clinical samples Having established a possible role of SENV in some pathological conditions further extended clinical studies were carried out. Selected clinical samples have been screened by PCR. First a PCR capable of amplifying simultaneously SENV-A, SENV- B, SENV-C and SENV-D sequences was optimized: To this end, primer BCD 1 S (SEQ ID NO: 97) was modified and the resulting primer NEW BCD 1S (SEQ ID NO: 115) was used in combination with primer L 2AS (SEQ ID NO: 71), respectively, derived from conserved sequences among SENV-A, SENV- B, SENV-C and SENV-D. These reactions were carried out as described before (see example 9). PCR consisted of preheating at 94°C for 5 min, 40 cycles of 94°C for 1 min, 52°C for 1 min and 72°C for 1 min, and an incubation at 72°C for 7 min. In order to evaluate the specificity of the amplified products, aliquots of 5 μl of each amplified product were hybridized in DEIA assay (Mantero, loc. cit.) with the following biotinylated probes: a SEN specific (SEQ ID NO: 98) specific for a conserved sequence in the middle within the amplified DNA, LA (SEQ ID NO: 99), specific for SENV-A sequences, LB (SEQ ID NO: 100), specific for SENV-B sequences, LC (SEQ ID NO: 101 ), specific for SENV-C sequences, LD (SEQ ID NO: 102), specific for SENV-D sequences. Thus, each amplified product could be simultaneously tested for the presence of total SENV sequences as well as for each specific genotype/subtype. Sera from the specific, highly selected patient groups were analyzed. Data are represented in Figure 54. One group (patients No: 1 to 12) comprised individuals that developed acute Non A-Non E (NANE, post transfusion) hepatitis after a single blood transfusion. The second group (patients No: 13 to 22) comprised individuals with chronic Non A-Non E hepatitis (NANE, chronic hepatitis), while the third group (patients No: 23 to 31) (HCV positive donors) consisted of blood donors infected with hepatitis C virus (HCV). Finally, 20 healthy blood donors were included in the analysis (patient No. 32 to 52). The results in Figure 54 show the values obtained by amplification of the samples with primers NEW BCD 1 S (SEQ ID NO: 115) and L 2AS (SEQ ID NO: 71). The values are expressed as optical density values. It is evident from the data that there is a very strong correlation between SENV and hepatitis transmission although very few blood donors resulted also positive for SENV. Considering the heterogenicity of SENV viruses, the possibility that some SENV subtypes may be more pathogenic than others is contemplated. In order to verify this assumption, several PCR amplicons from acute Non A-Non E patients (NANE) as well as of amplicons obtained from healthy blood donors were sequenced. Interestingly, all the three SENV positive, healthy blood donors exclusively harbored SENV-B sequences while the situation was much different in the acute hepatitis patients. Three of them (patient 2, 7 and 9) were infected with SENV-D virus while patient 5 contained exclusively SENV-A sequences. Patients 6, 8, 10 and 12 (see Figure 54) contained identical SENV sequences. However, this sequence (SEQ ID NO: 1 16) could not be related to any of the known SENV subtype. Thus, SEQ ID NO: 116 identifies a new SENV variant. Patient 1 also harbored a new SENV variant but its sequence (SEQ ID NO: 117) was different from the one detected in patients 6, 8, 10 and 12. These data show that SENV can transmit hepatitis through transfusion, furthermore the data also indicate that some SENV subtypes are more pathogenic than others. SENV-B, for instance, has been found in healthy blood donors and therefore its potential role in transmitting disease appears to be marginal. On the contrary SENV- A, SENV-D and SENV-E are very rarely detected in healthy blood donors, however, they appear to be associated with hepatitis transmission. Example 18 Identification and molecular characterization of SENV-E Although the vast majority of SENV sequences detected in patient 7 belong to SENV- A subtype, a clone containing a new, different SENV sequence was identified in this patient. In order to obtain the complete sequence of this new SEN virus, termed SENV-E, two different PCR reactions were set up: First, primers L 2AS (SEQ ID NO: 71) and TTV15S (SEQ ID NO: 72), respectively, were used. These were derived from the available sequence of SENV-D (SEQ ID NO: 53) and from the most 5' region of the TTV sequence. Second, primers NEW BCD 1S (SEQ ID NO: 115) derived from the available sequence of SEN-D (SEQ ID NO: 53) and primer 662AS (SEQ ID NO: 86), derived from the 3' sequence of SENV- C were used. Since SENV-A, SENV-B and SENV-C share a common sequence in the 3' untranslated region of their genomes, it was likely that a region of sequence similarity would also exist in the most 3' region of the genomes of SENV-C and SENV-E. PCR was carried out as described hereinabove and consisted of a preheating at 94°C for 5 min, 45 cycles of 94°C for 1 min, 58°C for 1 min, and 72°C for 1 min, and an incubation at 72°C for 7 min. Employing this strategy, two amplicons of about 1350 and 1614 bp were obtained. As described hereinabove, gel slices corresponding to these 1350 bp and 1914 bands were cut out and purified DNA extracts were connected to a pGEM vector (Promega, Madison, WI, USA) according to standard protocols and introduced to E. coli. The DNA sequences of the inserts were determined by using the AutoRead sequencing Kit (Pharmacia Biotech) with fluorescent M13 Universal primer and fluorescent M13 Reverse. Sequences were determined on three clones of the respective PCR products, and the consensus sequence was adopted. Using this strategy, several clones that overlapped the 5' and 3' regions of the available SENV-E sequence were obtained. After assembling the overlapping sequences with the ASSEMLGEL program, an unique sequence of 3263 bases was obtained. This sequence was named SENV-E (SEQ ID NO: 118). As all the other SEN viruses, SENV-E contains three open reading frames (ORF1 , ORF2 and ORF3) respectively of 743, 152 and 97 amino acids (SEQ ID NOs: 122, 123 and 124). SEQ ID NO: 125 relates to the nucleotide sequence of SENV-E, excluding the 5' and 3' portions which are highly homologous to TTV. The alignment of the amino acid sequences encoding for the major ORF (ORF1) of SENV-E with the one of SENV-A, SENV-B, SENV-C, SENV-D and of TTV demonstrated that these protein sequences share 47.35%, 42.86%, 44.68%, 44.82% and 35.53% of identity, respectively. At the nucleotide level the identity of this ORF1 are 53.97%, 54.17%, 53.40%, 54.00% and 48.12%, respectively. The alignment of the amino acid sequences encoding for the ORF2 of SENV-E with ORF2 of SENV-A, SENV-B, SENV-C, SENV-D and of TTV demonstrated that these sequences share 45.39%, 34.21%, 46.71%, 33.55% and 31.58% of identity, respectively. At the nucleotide level, these identities are 61 ,32%, 54.73%, 57.58%, 53.63% and 52.09%, respectively. Finally, a comparison of the ORF3 of SENV-E with the ORF3 of SENV-A, SENV-B, SENV-C and SENV-D demonstrated that these sequences share 30.23%, 27.71%, 31.82% and 25.00% of identity, respectively. At the nucleotide level, these indentities are 52.19%, 56.22%, 52.43 % and 54.68%, respectively. These data show that SENV-E is indeed a member of the SENV family, although it appears to be more distantly related to the other members of said family, which have, so far, been identified. The phylogenetic distances between the ORF1 proteins, estimated by the PROTDIST program of the PHYLIP package, (Figure 55) revealed that SENV-E is the most divergent among the SEN viruses so far identified. However, SENV-E is still more closely related to the other four identified SENV (A to D) than TTV (see Figure 55). Example 19 Different biological effects of SENV subtypes Given the high level of structural diversity among the SENV subtypes so far identified, it was investigated whether such diversity could also result in differential biological effects. To this end the incidence of SENV-A, SENV-B, SENV-C and SENV-D in different groups of patients affected by different diseases was studied. DNA samples (extracted from the different patients) were amplified by PCR with primers NEW BCD 1S (SEQ ID NO: 115) and primer L 2AS (SEQ ID NO: 71). Again, this PCR reactions were carried out as described hereinabove and consisted of a preheating at 94°C for 5 min, 40 cycles of 94°C for 1 min, 54°C for 1 min, and 72°C for 1 min, and an incubation at 72°C for 7 min. The specificity of the amplified products was tested as described above in a DEIA assay (Mantero, loc. cit.) employing the following biotinylated probes: LA (SEQ ID NO: 96), specific for SENV-A sequences, LB (SEQ ID NO: 97), specific for SENV-B sequences, LC (SEQ ID NO: 98), specific for SENV-C sequences, LD (SEQ ID NO: 99), specific for SENV-D sequences. The results in Figure 56 show the percentage of patients harboring SENV-A. SENV-A was not detected in patients suffering from several diseases, like neurological disorders and rheumathoid arthritis neither in healthy blood donors. However, this virus was present in a high proportion of groups of patients that have received exogenous blood demonstrating the parenteral route of transmission of this agent. Surprisingly, SENV-A was also found to be present in a high proportion of patients affected by Crohn's disease and hepatocarcinomas. Thus, this particular viral agent may be involved in Crohn's disease, a pathology of unknown etiology for which the involvement of a transmissible agent is suspected. Figure 57 shows the incidence of SENV-B in the different groups of patients. It is evident that the profile of the positive samples is very different from the one obtained from SENV-A. It is striking, for instance, that the percentage of SENV-B positive samples among HIV+ intravenous drug users (IVDU) is by far much lower as compared to SENV-A. Furthermore, SENV-B appears to be randomly present also in categories of patients not exposed to exogenous blood. The data in Figure 58 and 59 show the distribution of SENV-C and SENV-D in patient samples. Again, the distributions of these viral subtypes in the different groups varied considerably. Both SENV-C and SENV-D were detected in a considerable proportion of patients with Lupus erythematosus. Interestingly, these two viral subtypes are, however, practically absent in the cohort of rheumatoid arthritis patients. Thus, it is likely that SENV-C and SENV-D may be involved in the transmission or in the maintenance of the Lupus condition. It can be concluded that the members of the SENV family have (a) different biological or biomedicai implication(s). Most importantly, the type of disease to which they can be associated appears to be rather manifold: SENV-A and SENV-D appear to be strongly associated to the transmission of hepatitis of unknown etiology. Furthermore, SENV-A appears to be also associated to Crohn's disease. SENV-C and SENV-D, on the other hand, appear to play an important role in Lupus erythematosus. Finally, the different percentages of positive samples observed in the groups of patients exposed to exogenous blood may also indicate that either the different SENV subtypes have different routes of transmission or, alternatively, that they induce in the host a different type of immune response. It is of note, that SENV-B appears not to be related to any of the screened pathological conditions. Example 20 Development of a SENV-A and SENV-D specific PCR Having established that the different SENV subtypes exhibit different and pathogenetical features, it was important to develop specific tests in order to analyze and detect them individually. Example 6 describes a method for selectively amplifying and detecting SENV-A. By aligning additional SENV-A sequences it was found that a new set of primers is also suitable for SENV-A amplification. This new set of primers was named NEW SEN 3S (SEQ ID NO: 126) and NEW SEN 2AS (SEQ ID NO: 127). These primers were used in PCR reactions (Reaction 1) as described in example 6. The specificity of the amplified products was assessed in a DEIA assay using the SEN 37 biotinylated probe (SEQ ID NO: 13). Furthermore, a method for selectively amplifying and detecting SENV-D was developed. To this end all the available SENV sequences were aligned and primers and a specific probe for SENV-D were identified. DNA extracted from the different patients infected with SENV-A, SENV-B, SENV-C and SENV-D was amplified by PCR with primers D10S (SEQ ID NO: 128) and primer L 2AS (SEQ ID NO: 71) (Reaction 2) or with primers D10S (SEQ ID NO: 128) and primer D2AS (SEQ ID NO: 129) (Reaction 3). The PCR was carried out as described hereinabove and consisted of a preheating at 94°C for 5 min, 40 cycles of 94°C for 1 min, 58°C for 1 min, and 72°C for 1 min, and an incubation at 72°C for 7 min. In order to verify the specificity of the amplified products, aliquots of 5 μl of each amplified products were hybridized in the above mentioned DEIA assay with the biotinylated probe New D Biot (SEQ ID NO: 130) internal to the amplicons generated both by reaction 2 and reaction 3. The data in Figure 60 shows that reaction 1 selectively amplified SENV-A positive samples and not those containing SENV-B, SENV-C and SENV-D. On the contrary, reactions 2 and 3 selectively amplified SENV-D positive samples but not samples positive for SENV-A, SENV-B and SENV-C. These data show that the use of highly specific primers and probes (e.g., SEQ ID NOs: 126 to 130) allow for the specific detection of SENV-A and SENV-D in any given test sample. Example 21. Cloning and expression steps of ORF1 SENV-A protein Construction of the recombinant expression plasmid: The ORF1 of SENV-A was cloned into the pGEM®-T Easy and amplified by PCR in order to add two unique restriction site sequences at the 5' and the 3' end. This allowed the cloning of the sequence into the pET-30a expression vector (Novagen). PCR reaction was carried out in a volume of 100 μl using the Perkin-Elmer GeneAmp® kit containing 10mM Tris-HCl pH 8.3, 50 mM KCI, 1.5 mM MgCI 2 , 0.001% gelatin, 0.2 mM of dNTP mixture and 40 pmoles of the forward primer: TTG GAT CCA TGA ACT ATG CCA TGC ACT GCG (SEQ ID NO:109) and 40 pmoles of the reverse primer: ATG AAT TCT TAC GTG AGG TGT GCT AAA GAT AGT GGG (SEQ ID NO:110). The PCR reaction was performed in a Perkin-Elmer DNA thermal cycler 480 and the amplification reaction consisted in 1 cycle: 94°C 3', 57°C 1 ', 72°C 3' and 30 cycles: 94°C 1', 57°C 1', 72°C 3'. The amplicon obtained had a size of 1930 bp and was cloned into the EcoRI-BamHI site of pET30a E.coli expression vector (Novagen). Expression and purification of the recombinant protein: After a first step of recombinant plasmid amplification in E. coli XL1 Blue cells (Stratagene cat # 200249) , the pET30aORF1 plasmid was transferred to E. coli strain BL21 (DE3) for protein production. The induction protocol was performed according to the pET system manual (Novagen): an overnight culture of recombinant E. coli was inoculated at a 1 :50 dilution into fresh Luria broth plus kanamycin (30 μg/ml); the cells were incubated under shaking at 37°C until the culture reaches 0.6 OD 6 oo- The ceils were then induced adding IPTG from a 100mM stock to a final concentration of 1 mM. After 3 hours of induction the cells were centrifuged and a protein extraction step was carried out after an overnight standing of the cellular pellet at -20°C. The protein extraction was performed in three steps in order to separate the soluble and the insoluble protein fractions: the first step involved the extraction of soluble proteins with a phosphate buffer (20mM NaH 2 P0 4 ; 0.5M NaCl pH 7.4) and sonication 4x1 min. at 250W. After centrifugation at 9000g for 30' at 4°C, the supernatant was kept as soluble protein fraction, while the pellet was resuspended in a urea buffer (8M urea; 100mM NaCl; 20mM Na 2 HP0 4 pH 7.0), sonicated 2x1 min at 250 W, heated at 70°C for 10' and then centrifuged at 9000g for 30' at 4°C. The remaining pellet was again solubilized in 8M urea, recentrifuged and the residual pellet (if present) was resuspended in SDS-PAGE loading buffer containing 0.1 % SDS. The recombinant ORF1 protein was recovered mainly in the urea fraction and loaded onto a nickel column for purification (HI TRAP Chelating Pharmacia, #17-0409-01 , used according to the manufacturer's protocols). Using an imidazole concentration of 500mM, a partially purified fusion protein of 80354 Dalton was obtained (SEQ ID NO:103 and SEQ ID NO:104). The pools have been obtained by eluting the column with linear gradient of 500mM Imidazole solution. Antigen preparations were electrophoresed in 10% acrylamide slab gels using sodium dodecyl sulfate. The gel was run at 130V at room temperature until the tracking dye reached the bottom of the gel. The gel was then transferred to nitrocellulose paper. The electrophoretic blot was first soaked in PBS containing 0.05% casein for 20min and then incubated with serum n°2174 (a serum from a haemophilic, poly-transfused patient which was PCR-positive for SENV-A) diluted 1 :100 in PBS containing 0.05% casein for 1 hour at 37°C. The nitrocellulose sheet was washed three times in PBS and incubated with horseradish peroxidase- conjugate goat anti-human-lgG at a dilution of 1 :500 in PBS containing 0.05% casein for 1 hour at 37°C. The blot was again washed three times in PBS. The development was done with 4- Cl-Naphtol and stopped by washing in methanol. The nitrocellulose was stored protected from light. Anti-ORF1 SENV-A IgG antibodies present in the 2174 serum reacted strongly with a 81000 m.w. protein. Fractions, which contained recombinant SENV-A ORF1 (pORF1 ) as detected by this Western blot method were collected and were further used for ELISA assay development. Example 22. Cloning and expression steps of ORF2 SENV-A protein Construction of the recombinant expression plasmid: The ORF2 of SENV-A was cloned into the pGEM®-T Easy and amplified by PCR in order to add two unique restriction site sequences at the 5' and the 3' end. This allowed the cloning of the sequence into the pET-30a expression vector (Novagen). PCR reaction was carried out in a volume of 100 μl using the Perkin-Elmer GeneAmp® kit containing 10mM Tris-HCl pH 8.3, 50 mM KCI, 1.5 mM MgCI 2 , 0.001% gelatin, 0.2 mM of dNTP mixture and 40 pmoles of the forward primer: ATG GAT CCG GGC TAT GGG CAA GGC TCT TAG GG (SEQ ID NO:111 ) and 40 pmoles of the reverse primer: TAG AAT TCT TAC TGT TGG TCG TCT TCT TCG ACG G (SEQ ID NO:112). The PCR reaction was performed in a Perkin-Elmer DNA thermal cycler 480 and the amplification reaction consisted in 1 cycle: 94°C 3', 60°C 1 ', 72°C 3' and 30 cycles: 94°C 1 ', 60°C 1 ', 72°C 2'. The amplicon obtained had a size of 1930 bp and was cloned into the EcoRI-BamHI site of pET30a E.coli expression vector (Novagen). Expression and purification of the recombinant protein: After a first step of recombinant plasmid amplification in E. coli XL1 Blue cells (Stratagene cat # 200249), the pET30cORF2 plasmid was transferred to E. coli strain BL21 (DE3) for protein production. The induction protocol was performed according to the pET system manual (Novagen): an overnight culture of recombinant E. coli was inoculated at a 1 :50 dilution into fresh Luria broth plus kanamycin (30 μg/ml); the cells were incubated under shaking at 37°C until the culture reaches 0.6 OD 6 oo- The cells were then induced adding IPTG from a 100mM stock to a final concentration of 1 mM. After 3 hours of induction the cells were centrifuged and a protein extraction step was carried out after an overnight standing of the cellular pellet at -20°C. The protein extraction was performed in three steps in order to separate the soluble and the insoluble protein fractions: the first step involved the extraction of soluble proteins with a phosphate buffer (20mM NaH 2 P0 4 ; 0.5M NaCl pH 7.4) and sonication 4x1 min. at 250W. After centrifugation at 9000g for 30' at 4°C, the supernatant was kept as soluble protein fraction, while the pellet was resuspended in a urea buffer (8M urea; 100mM NaCl; 20mM Na 2 HP0 pH 7.0), sonicated 2x1 min at 250 W, heated at 70°C for 10' and then centrifuged at 9000g for 30' at 4°C. The obtained pellet was again solubilized in 8M urea and repelleted. The residual pellet (if present) was resuspended in SDS-PAGE loading buffer. The recombinant ORF1 protein was recovered mainly in the urea fraction and loaded onto a nickel column for purification (HI TRAP Chelating Pharmacia, #17-0409-01 , used according to the manufacturer's protocols). Using an imidazole concentration of 500mM, a partially purified fusion protein of 24000 dalton molecular weight (SEQ ID NO:105 and SEQ ID NO:106). The pools have been obtained by eluting the column with linear gradient of 500mM Imidazole solution. Antigen preparations were electrophoresed in 10% acrylamide slab gels using sodium dodecyl sulfate. The gel was run at 130V at room temperature until the tracking dye reached the bottom of the gel. The gel was then transferred to nitrocellulose paper. The electrophoretic blot was first soaked in PBS containing 0.05% casein for 20min and then incubated with serum n°2174 (PCR-positive for SENV-A) diluted 1 :100 in PBS containing 0.05% casein for 1 hour at 37°C. The nitrocellulose sheet was washed three times in PBS and incubated with horseradish peroxidase-conjugate goat anti-human-lgG at a dilution of 1 :500 in PBS containing 0.05% casein for 1 hour at 37°C. The blot was again washed three times in PBS. The development was done with 4- CI-Naphtol and stopped by washing in methanol. The nitrocellulose was stored protected from light. In figure 61 results of the immunochemical analysis are reported. IgG antibodies present in the serum reacted strongly with the 30000 m.w protein. The pORF2-containing fractions, as defined by this Western blot techniques, were further used for ELISA assay development. Example 23 Cloning and expression steps of ORF3 SENV-A protein Construction of the recombinant expression plasmid: The ORF3 of SENV-A was cloned into the pGEM®-T Easy and amplified by PCR in order to add two unique restriction site sequences at the 5' and the 3' end. This allowed the cloning of the sequence into the pET-30b expression vector (Novagen). PCR reaction was carried out in a volume of 100 μl using the Perkin-Elmer GeneAmp® kit containing 10mM Tris-HCl pH 8.3, 50 mM KCI, 1.5 mM MgCI 2 , 0.001 % gelatin, 0.2 mM of dNTP mixture and 40 pmoles of the forward primer: ATG GAT CCC CAA CAG TAG ATG AAC TCT ATC TTC AAA AAC C (SEQ ID NO:113)and 40 pmoles of the reverse primer: TAG AAT TCT GGA ACA TGT CAT ACT TTA CGT GAG GTG TGC (SEQ ID NO:114).The PCR reaction was performed in a Perkin-Elmer DNA thermal cycler 480 and the amplification reaction consisted in 1 cycle: 94°C 3'. 64°C 1 ', 72°C 3' and 30 cycles: 94°C 1 ', 64°C 1 ', 72°C 1 '. The amplicon thus obtained had a size of 321 bp and has been cloned into the EcoRI-BamHI site of pET30b E.coli expression vector (Novagen). Expression and purification of the recombinant protein: After a first step of recombinant plasmid amplification in E. coli XL1 Blue cells (Stratagene cat # 200249) , the pET30aORF1 plasmid was transferred to E. coli strain BL21 (DE3) for protein production. The induction protocol was performed according to the pET system manual (Novagen): an overnight culture of recombinant E. coli was inoculated at a 1 :50 dilution into fresh Luria broth plus kanamycin (30 μg/ml); the cells were incubated under shaking at 37°C until the culture reaches 0.6 OD 60 o. The cells were then induced adding IPTG from a 100mM stock to a final concentration of 1 mM. After 3 hours of induction the cells were centrifuged and a protein extraction step was carried out after an overnight standing of the cellular pellet at -20°C. The protein extraction was performed in three steps in order to separate the soluble and the insoluble protein fractions: the first step involved the extraction of soluble proteins with a phosphate buffer (20mM NaH 2 P0 4 ; 0.5M NaCl pH 7.4) and sonication 4x1 min. at 250W. After centrifugation at 9000g for 30' at 4°C, the supernatant was kept as soluble protein fraction, while the pellet was resuspended in a urea buffer (8M urea; 100mM NaCl; 20mM Na 2 HP0 4 pH 7.0), sonicated 2x1 min at 250 W, heated at 70°C for 10' and then centrifuged at 9000g for 30' at 4°C. After resolubilization in 8M urea, the pellet fraction was again centrifuged and the residual pellet (if present) was resuspended in SDS-PAGE loading buffer. The recombinant ORF1 protein was recovered mainly in the urea fraction and loaded onto a nickel column for purification (HI TRAP Chelating Pharmacia, #17-0409-01 , used according to the manufacturer's protocols). Using an imidazole concentration of 500mM, a partially purified fusion protein of 15000 daltons of molecular weight has been obtained (SEQ ID NO: 107 and SEQ ID NO:108). Antigen preparations were electrophoresed in 10% acrylamide slab gels using sodium dodecyl sulfate. The gel was run at 130V at room temperature until the tracking dye reached the bottom of the gel. The gel was then transferred to nitrocellulose paper. The electrophoretic blot was first soaked in PBS containing 0.05% casein for 20min and then incubated with serum n°2174 (SENV-A positive in PCR assay) diluted 1 :100 in PBS containing 0.05% casein for 1 hour at 37°C. The nitrocellulose sheet was washed three times in PBS and incubated with horseradish peroxidase-conjugate goat anti-human-lgG at a dilution of 1 :500 in PBS containing 0.05% casein for 1 hour at 37°C. The blot was again washed three times in PBS. The development was done with 4- Cl-Naphtol and stopped by washing in methanol. The nitrocellulose was stored protected from light. Fractions containing recombinant ORF3 from SENV-A pORF3, as determined by this Western blot technique, were further used for ELISA assay development. Example 24 Cloning and expression steps of ORF2 SENV-D protein Construction of the recombinant expression plasmid: SENV-D ORF2 cloned into the pGEM®-T Easy was amplified by PCR in order to add two unique restriction site sequences at the 5' and the 3' end which allowed the cloning of the sequence into a pET24a expression vector (Novagen). The forward primer had a non-complementary EcoRl recognition sequence at the 5' end (GGG AAT TCG GGC TCT GGG CAA GGC TCT T, SEQ ID NO: 131), whilst the reverse primer had a non-complementary Hind III recognition sequence at the 5' end (TTC AAG CTT ACT GTT GGT CTT CTT CGA CGG CG, SEQ ID NO: 132). PCR reaction was carried out in a volume of 100 μl using the Taq DNA Polymerase in storage buffer A (Promega,), Thermophilic DNA Polymerase 10X buffer magnesium free (Promega - it has a composition of 10 mM Tris-HCl pH 9 at 25°C, 50 mM KCI and 0.1% Triton® X-100), 1.5 mM magnesium chloride solution (Promega), 0.2 mM of dNTP mixture (Perkin-Elmer GeneAmp®kit) and 20 pmoles of both primers. The PCR was performed for 35 cycles (94°C, 1'; 59°C, 1 '; 72°C, 1'; with additional 20' for the last cycle) and the amplification products measured 512 bp. The PCR product was digested by restriction enzymes EcoRl and Hind III (New England Biolab) and ligated to pET24a expression vector (Novagen). SEQ ID NO: 133 is shown in table 4. TABLE 4 RECOMBINANT ORF2 D Nucleotide sequence (SEQ ID NO: 133) ATGGCTAGCATGACTGGTGGACAGCAAATGGGTCGCGGATCCGAATTCGGGCTCTGGGCAAG GCTCTTAAAAATGCACTTTTCTAAAATAACCAGAAAGAAAAGGAAACTGCTACTGCAAACTG TGCCGCTTCCAAAGAGCCAACGGACTACCATGAGCTGGTCCAGACCCGTGCAAAATGTTTCT ATTTGTGAACAACACTGGTTTAAGTCCTGCCTTCAATCACACGCATGCTTTTGTGGCTGTAA TAATCCTGTTATTCATTTTAACAACATTGCTACTCGCTTTAACTATCTGCCTACTGCCAATC CGCCTGTGGGACCCTCCCAACCGCCCACACGCCCGCCGTCCCGCTTGAGACCCCTTYCCGCT CTCCCCGCGCCTCCCGCTGATCCACAAGCACCATGGCCTGGGGCTGGTGGCTCAAGCGGTGG AGGAGAAGAAAGAAACCAGCGTGGAAGAAGTGGAGAACGCGCAGATGGAGAAGATTTCGACG CAGAAGACCTAGACGCACTTATGGCCGCCGTCGAAGAAGACCAACAGTAAGCTTGCGGCCGC ACTCGAGCACCACCACCACCACCACTGA Y=C or T Bold and underlined: the 1 st ATG of the ORF2 sequence underlined: stop codon of the ORF2 sequence Expression and purification of the recombinant protein: After a first step of recombinant plasmid amplification in E.coli XL1 Blue strain competent cells (Stratagene, #200249), the pET24a-ORF2 plasmid was transferred to E.coli BL21 (DE3) (F ompT gal dcm (DE3) .Novagen) competent cells for recombinant protein production. The induction protocol of transformed E.coli BL21 (DE3) strain was performed according to the pET system manual (Novagen); an overnight culture of recombinant E. coli was inoculated at a 1 :50 diluition into fresh Luria-Bertani broth (Molecular Cloning - A Laboratory Manual - Sambrook.Fritch, Maniatis) plus kanamycin (30μg/ml); the cells were incubated under shaking at 37°C until the culture reaches 0.7 OD 59 o-The cells were then induced adding IPTG from a 100 mM stock to a final concentration of 1 mM. After 3 hours of induction the cells were centrifuged and a protein extraction step has been carried out after an overnight standing of the cellular pellet at -80°C. The protein extraction was performed according to the procedure described below in order to separate the recombinant fusion protein ORF2 produced in insoluble ("inclusion body") form. The recombinant ORF2 protein was recovered in the 8M urea fraction (buffer C: 50 mM TRIS-HCI; pH 9, 1 mM EDTA, 8M urea, 14 mM βOH, 100 mM NaCl). After 3 hours of induction the cells were centrifuged at 4000 rpm for 30' at 4°C and the supernatant was discarded. The weight of the E. coli BL21 pellet was determined and for each gram (wet weigh) of E. coli, 10 ml of STET buffer (Sucrose, 10mM Tris, 1 mM EDTA, 5% Triton-X) were added in order to resuspend the pellet; stirring overnight at 4°C the suspension of cells in buffer STET plus 130μl of lisozyme (10mg/ml) for each gram (wet weigh) of E. coli pellet. The cell lysate was centrifuged at 14.000 rpm for 20' at 4°C to separate the inclusion bodies from the cellular fragments. After this step the supernatant was removed and the inclusion body pellets of ORF2 protein was purified using a multiple washing technique. The pellet was resuspended in buffer A (50 mM TRIS-HCI; pH8 volume = volume buffer STET) and centrifuged at 14.000 rpm for 20' at 4°C, then the supernatant was removed. The pellet was resuspended in buffer A; stirring for three hours at 37°C the suspension of inclusion bodies in buffer A plus 10μl of benzonase per ml of buffer A and MgCI 2 from a 100 mM stock solution to final concentration of 1 mM. After 3 hours of stirring the cell lysate was centrifuged at 14.000 rpm for 20' at 4°C; the supernatant was discarded and the pellet was resuspended in buffer A and centrifuged at 14.000 rpm for 20' at 4°C. The supernatant was discarded and the pellet was resuspended in buffer B (100 mM TRIS-HCI; pH 9; 4M urea, (87%) 10% glycerol, 14mM βOH; added 5ml for each gram of E. coli pellet) and stirring overnight at 4°C. Then the cell lysate was centrifuged at 14.000 rpm for 20' at 4°C; the supernatant was removed and the pellet has been resuspended in buffer C (50 mM TRIS-HCI, pH 9, 8M urea, (87%) 10% glycerol, 14mM βOH, 1 mM EDTA, added 5ml for each gram of E. coli pellet). From every steps samples (10μl) and mixed each with 10μl of 2X SDS gel-loading buffer and analyze by SDS-polyacrylamide gel electrophoresis. Table 5 RECOMBINANT ORF2 D Protein sequence (SEQ ID NO: 134) MASMTGGQQMGRGSEFG WARLLKMHFSKITIUααiKLLLQ VPLPKSQRTTMS SRPVQNVS ICEQH FKSCLQSHACFCGCNNPVIHFN IATRFNYLPTANPPVGPSQPPTRPPSRLRPLXA LPAPPADPQAP PGAGGSSGGGEERNQRGRSGERADGEDFDAEDLDALMAAVEEDQQ bold:protein sequence of the ORF2 X: S or P Example 25 Cloning and expression steps of ORF3 SENV-D protein Construction of the recombinant expression plasmid: SENV-D ORF3 cloned into the pGEM®-T Easy was amplified by PCR in order to add two unique restriction site sequences at the 5' and the 3' end which allowed the cloning of the sequence into a pET24a expression vector (Novagen). The forward primer had a non-complementary EcoRl recognition sequence at the 5' end (GGA ATT CAC GAT GAA CAG ATT GAT GTT CCA GAC TTT ACA GA, SEQ ID NO: 135), whilst the reverse primer had a non-complementary Hind III recognition sequence at the 5' end (CCC AAG CTT AAT GTA AAT TTG CTTT GGT TTT CTG GAG TTG G, SEQ ID NO: 136). PCR reaction was carried out in a volume of 100 μl using the Taq DNA Polymerase in storage buffer A (Promega,), Thermophiiic DNA Polymerase 10X buffer magnesium free (Promega - it has a composition of 10 mM Tris-HCl pH 9 at 25°C, 50 mM KCI and 0.1 % Triton® X-100), 1.5 mM magnesium chloride solution (Promega), 0.2 mM of dNTP mixture (Perkin-Elmer GeneAmp®kit) and 20 pmoles of both primers. The PCR was performed for 35 cycles (94°C, 1 "; 59°C, 1'; 72°C, 1 '; with additional 20' for the last cycle) and the amplification products measured 512 bp. The PCR product was digested by restriction enzymes EcoRl and Hind III (New England Biolab) and ligated to pET24a expression vector (Novagen). SEQ ID NO: 137 is shown in table 7. TABLE 7 RECOMBINANT ORF3 D Nucleotide sequence (SEQ ID NO: 137) ATGGCTAGCATGACTGGTGGACAGCAAATGGGTCGCGGATCCGAATTCACGATGAACAGATT GATGTTCCAGACTTTACAGAACAGCCTAAAATCCCCCGACTTTTCCCCCCAGTCGAACTCAA AGAAAGGGAAGAAAAAGACTCAGGTTCGGAGACGGAGAGCATCAGCAGCTCCCAAGAAAAAG AAGCACAAAAGCAAGCGGCGCTACCAGTCCAGCAGCAGCTCCGACTCCAACTGCGAGAACAA CAGCGACTCCGAGTCCACTTGCAGCACCTCTTCCTCCAACTCCAGAAAACCAAAGCAAATTT ACATTAAGCTTGCGGCCGCACTCGAGCACCACCACCACCACCACTGA Bold, underlined: the 1 st ATG of the ORF3 sequence Underlined: Stop-Codon of ORF3 sequence Expression of the recombinant protein: After a first step of recombinant plasmid amplification in E.coli XL1 Blue strain competent cells (Stratagene, #200249), the pET24a-ORF3 plasmid was transferred to E. coli BL21 (DE3) (F " ompT /?sαfSB(rB " mB " ) gal dcm (DE3) , Novagen) competent cells for recombinant protein production. The induction protocol of transformed E. coli BL21 (DE3) strain was performed according to the pET system manual (Novagen). Table 8 RECOMBINANT ORF3 D Protein sequence (SEQ ID NO: 138) MASMTGGQQMGRGSEFTl^R MFQTLQNSLKSPDFSPQSNSIOζGKKKTQvllRRRASAAPKKK KHKSKRRYQSSSSSDSNCENNSDSESTCSTSSSNSRKPKQIYIKLAAA EHHHHHH bold: ORF3 protein sequence Example 26 Detection of SENV-A antibodies by serological method The method used for the determination of anti SENV-A antibodies was an indirect sandwich immunoassay; plates were passively coated with the three recombinant SENV-A antigens (ORF1 , ORF2 and ORF3) using a carbonate buffer solution (2.93 g/l NaHC0 3 , 1.56 g/l Na 2 C0 3 , pH 9,6 + 0.2); 150 μl of the coating solution were added into the wells of the microplate and incubated overnight. After the removal of the coating solution, 300 μl of post-coating solution was dispensed (0.1 M Tris-HCl, 6.7 ml/l BSA 30%, pH 7.4). After 1-3 hours of incubation 300 μl of fixing solution (40 g/l PVP, 100 g/l sucrose) were added into the wells and further incubated 1 -3 hours at room temperature. Finally, coated plates were sealed and stored at 4° C until use. The serum samples were diluted before testing 1 :101 using sample diluent solution containing 1.15 g/l Na 2 HP0 4 , 2H 2 0, 0.16 g/l KH 2 P0 4 , 6.40 g/l NaCl, 0.16 g/l KCI, 2 ml/l Proclin 300, 200 U/ml Penicilline-Streptomicine, 32 g/l Bovine serum albumin frac. V, 2 ml/l Tween 20, 2 g/l Triton X 705, 1 g/l EDTANa 2 , pH 7.4. Serum samples were incubated for 1 hour + 5 minutes at 37° + 1 °C and then the plates were washed 5 times with wash buffer (9 g/l NaCl, 0.01 g/l Tween 20). The murine monoclonal antibody HP6017 anti-human IgG-HRP (obtained from Public Health Science Centre for Disease Control and Prevention, ATLANTA, USA) conjugate component is prepared just before use in a solution containing 12.24 g/l Trizma, 84.4 ml/l HCI 1 N, 8 g/l NaCl, 0.16 g/l KCI, 100 g/l Sucrose, 2 ml/l Proclin 300, 0.01 g/l Gentamicine, 20 mg/l HRP, 2.20 g/l CaCI2, 0.5 g/l Citocrome C, 40 g/l BSA Cristalline, pH 7.4). 100 μl of the conjugated solution were dispensed and incubated 1 hour ± 5 min at 37° C ± 1 ° C. Before the end of incubation, the chromogen/substrate solution was prepared by mixing the solution of chromogen (Tetramethylbenzidine derivative in citrate buffer) with substrate (hydrogen peroxide in citrate buffer) in amounts 1 :1. When the second incubation was completed the liquid was aspirated and all the wells were rinsed five times with wash buffer (9 g/l NaCl, 0.01 g/l Tween 20) ranging from 0.3 to 0.37 ml. After this washing step, 100 μl of chromogen/substrate were dispensed into the wells included the negative-control blank wells. The microplate was incubated for 30 ' + 2 minutes at room temperature, away from direct or intense light. At the end of incubation, 100 μl of blocking reagent (H 2 S0 4 1 N) were added into all wells, and the absorbance was determined with a photometer at 450/630 nm within one hour after the addition of the blocking reagent. Serum samples from 570 patients were collected and analyzed with this SENV-A ELISA assay. 284 were healthy blood donors collected at the US Red Cross (Rockville, MD), 43 were alcoholic cirrhotic patients (collected from Bioclinical Partners, MA, USA), 51 were samples from colon cancer patients (Istituto di Fisiologia Clinica, Pisa, Italy), 48 were from hemophiliacs and 49 samples were from HIV-HCV positive patients (collected from Bioclinical Partners, MA), 68 samples were from colorectal diseases patients (diverticulitis or benign adenomas, from Bioclinical Partners, MA), 29 from other cancers patients (breast, stomach, pancreas, from Istituto di Fisiologia Clinica, Pisa, Italy). The percentage of the SENV-A positive samples was the following: 3.2% for blood donors, 0.0% for other cancers, 2.0% for HIV-HCV positive patients, 3.0% for colorectal diseases. Then the percentage raised up to 8.3% for the hemophiliac patients, 11.6% for the cirrhosis patients and 33.3% for the colon cancer patients. As shown in table 9, the percentage of the positive samples observed in the various patient groups was compared to the percentage of positive subjects observed in the blood donors population by using the χ 2 test with one degree of freedom (PRIMER, "Statistica per discipline biomediche: programma applicativo" Stanton A. Glantz, copyright 1987 McGraw-Hill). Whilst the hemophiliacs, HCV-HIV positive, other cancers, colorectal patients did not differ significantly from the blood donors (P ranging from 0.20 to 0.74), there was a slight difference looking at the cirrhotic patients (P=0.032) and a significant difference with the colon cancers patients (P=0.000). Taken together these data showed the association of the presence of anti-SENV-A antibodies within the colon carcinoma patients cohort. Table 9. Statistical analysis by χ 2 test of serological data produced with the ELISA test (the wells have been coated with the mixture of all three ORFs of SENV-A). ! ? :% IE I BLOOD DONORS - ALCOHOLIC CIRRHOSIS |4,620 ι0,032 BLOOD DONORS - COLON CANCER 150,820 ,0,000 | BLOOD DONORS -» HEMOPHILIACS 1 ,700 ,0,192 BLOOD DONORS ;HIV-HCV POSITIVES ;o,ooι ;0,979 BLOOD DONORS - OTHER CANCERS ;o,152 ,0,697 BLOOD DONORS -» COLORECTAL DISEASES 0,111 0,739 Example 27 Epitope mapping of ORF2 of SENV-A In order to localize the immunological reactive areas of a given sequence of aminoacid a Pepscan analysis performed by Jerini BioTools (Berlin, Germany) was employed. The protein sequence was divided into 78 overlapping peptides. These segments are 13-mer long and have an overlapping region of 11 amino acids. The whole set of peptides was generated on a single cellulose membrane using the solid phase peptide synthesis method described herein below. Then the membrane was put in contact with a solution containing the appropriate reactive serum. After the development step the reactive areas of the protein was identified by detecting the reactive spots on the membrane. The amino acids for the peptide synthesis on cellulose purchased from Novabiochem (Bad Soden, Germany) and Bachem (Bubendoerf, Switzerland) were 9- fluorenylmethoxycarbonyl (Fmoc)-protected. The following side-chain protecting groups were used: trityl for C, H, N and Q; t-butyl for D, E, S and T; t-butoxycarbonyl for K; and pentamethylchroman sulfonyl for R. The cellulose membrane Wathman 540 paper (Maidstone, England) was used. Dimethylformamide (DMF), diisopropylcarbodiimide (DCI), N-methylimidazole (NMI), N-methylpyrrolidone (NMP), methanol, diisopropylethylamine (DIPA) were purchased from Fluka (Buchs, Switzerland). 2-(1 H-benzotriazole-1 -yl)-1 , 1 ,3,3- tertamethyluroniumtrafluoroborate (TBTU) was purchased from Novabiochem. The dried paper sheet was chemically modified in order to introduce suitable anchor functions for the subsequent peptide synthesis. In the first step, the membrane was treated without shaking for 3 h with 12 ml of a 0.20 M Fmoc-β-alanine solution (activated with 0.24 M DIC and 0.40 M NMI in DMF) to achieve an even distribution of amino function by esterification of activated β-alanine to the hydroxyl groups of the cellulose. After washing three times for 5 minutes with DMF, the Fmoc protecting groups were cleaved by treatment with 20% piperidine in DMF for 20 minutes. The membrane was washed with DMF (five times) and methanol (twice) and dried. In the following steps, 0.5-0.7 μl of a 0.3 M Fmoc protected aminoacid (activated with 0.3 M TBTU, 1 :1 in NMP) was spotted to predefined positions on the membrane using a glass or metal capillary (15-minutes reaction time). The remaining amino functions were acetylated by treatment of the membrane face down with 2% acetanhydride in DMF for 2 minutes and subsequently face up with 2% acetanhydride / 1% DIPA in DMF for 30 minutes. Then the membrane was washed four times with DMF and the Fmoc protecting groups have been removed by treatment with 20% piperidine in DMF for 20 minutes. The membrane was washed with DMF (five times) and the coupling/deprotecting steps with the next appropriate Fmoc aminoacid were repeated. After the last step the membrane was washed four times with DMF and twice with methanol and dried. The cellulose membrane coated with the overlapping peptides and the recombinant ORF2 SENV-A antigen to be used as a positive control has been washed with 80% methanol to fix all the polypeptides. Then the membrane has been blocked with PBS buffer containing 0.5% Casein, 0.02% Proclin-300 and 0.05 g/ml Sucrose for 1 hour at room temperature and stored at -20°C before use. In order to perform the epitope mapping assay, an anti-ORF2 SENV-A serum diluted 1 :5000 in PBS containing 0.5% Casein was incubated with the membrane for 3 hours, under shaking, after which the solution has been removed by aspiration and the membrane was rinsed 3 times for 10 minutes with wash buffer (Tris buffer saline containing 0.01 g/ml Tween). The washed membrane was treated with the murine monoclonal antibody HP6017 anti human IgG-HRP conjugate component is prepared just before use in a solution containing 12.24 g/l Trizma, 84.4 ml/l HCI 1 N, 8 g/l NaCl, 0.16 g/l KCI, 2 ml/l Proclin 300, 40 g/l BSA Cristalline, pH 7.4, then diluted 1 :10000 with PBS containing 0.5% Casein. 20ml of the conjugated solution are dispensed and incubated 1 hour + 5 min at room temperature and then rinsed three times as above. The membrane has been put in a transparent bag and 200 μl chromogen/substrate (BM chemiluminescence Blotting substrate (POD), Boehringer Mannheim) was added, the bag closed and the reaction proceeded for 1 minute. Then the liquid was aspirated, the bag with the membrane put in dark room, covered with a photograph plate (Kodak Biomax) for 35 sec. The plate was washed with GBX developer (Sigma #108h1394) for 2 minutes, subsequently rinsed with water and washed with a fixer solution (Sigma #98h1050) under stirring for 5 minutes. Reactivity was very intense with the ORF2 recombinant protein (full-length) and with peptides no. 61 , 62, 63 and 64 corresponding to sequences: peptide 61 PQWPGANDNTNTR SEQ ID NO: 139 peptide 62 WPGANDNTNTRAP SEQ ID NO: 140 peptide 63 GANDNTNTRAPTA SEQ ID NO: 141 peptide 64 D TNTRAPTAGE SEQ ID NO: 142 The common sequence among the peptides is NDNTNTR (SEQ ID NO : 143 ) corresponding to a linear epitope of ORF2 protein of SENV-A. The same procedure has been used for a negative serum (negative control) and no signal was obtained. Example 28 Mutational analysis of ORF2 of SENV-A In order to identify the so-called "key-residues" within the mapped epitope, the mutational analysis has been performed. Each aminoacid of the mapped epitope is substituted by all 20-L aminoacids to provide detailed information on the peptide binding. These peptides are synthesized on cellulose membrane as described in example 27 and can be incubated with the antibody in solution. Bound antibody is then detected on the cellulose membrane using standard immunoassay reaction (same procedure of example 27). Reactivity was very intense with the wild type epitope NDNTNTR (SEQ ID NO : 143 ) ; the key residues were: the asparagine at the amino terminus the aspartic acid in position 2 and the asparagine in position 3. These residues do not allow any substitution. The T in position 4 can be substituted by: the whole set of aminoacids but K and F The N in position 5 can be substituted by: A, F, G, K, L, M, N, F, R , S, T, Q, V, W, Y The T in position 6 can be substituted by: A, C, D, E, F, R and S The R in position 7 can be substituted by: D, E, K. Example 29 Epitope mapping of ORF1 of SENV-A The same procedure of example 27 has been used for the peptide synthesis and for the ELISA test. Reactivity was very intense with peptide n° 88 corresponding the following sequence: NKVIGFPMKGEEA (SEQ ID NO : 144 ) Positive signals have been obtained also with peptides n° 156, 157, 158 corresponding with this sequences: peptide N. 156 RYNTQFRPAYYDV SEQ ID NO: 145 peptide N. 157 NTQFRPAYYDVTY SEQ ID NO: 146 peptide N. 158 QFRPAYYDVTYNP SEQ ID NO: 147 The common sequence is QFRPAYYDV (SEQ ID NO : 148 ) Other positive signals from peptides n° 262, 263 corresponding to sequences: peptide 262 FHKFDTRRGFYSS SEQ ID NO: 149 peptide 263 KFDTRRGFYSSAS SEQ ID NO: 150 The common sequence is: KFDTRRGFYSS (SEQ ID NO : 151 ) Positive signals have been obtained with peptides n° 235, 236, 237, 238 corresponding to: peptide N. 235 CAMYSFKFLFGG SEQ ID NO: 152 peptide N. 236 AMYSFKFLFGGDL SEQ ID NO: 153 peptide N. 237 YSFKFLFGGDLLY SEQ ID NO : 154 peptide N. 238 FKFLFGGDLLYPQ SEQ ID NO: 155 The common sequence is: FKFLFGG (SEQ ID NO : 156 ) Positive signals have been recollected with peptides n° 206, 207 corresponding to: peptide 206 YVFYDTNFGNGKM SEQ ID NO: 157 peptide 207 FYDTNFGNGKMPS SEQ ID NO: 158 The common sequence is: FYDTNFGNGKM (SEQ ID NO : 159 ) The major epitopes for antigen from ORF 1 for SENV-A are therefore: NKVIGFPMKGEEA (SEQ ID NO: 144 ) QFRPAYYDV (SEQ ID NO : 148 ) KFDTRRGFYSS (SEQ ID NO : 151 ) FKFLFGG (SEQ ID NO : 156 ) FYDTNFGNGKM (SEQ ID NO : 159 ) Example 30 Epitope mapping of ORF2 of SENV-D The same procedure of example 27 has been used for the peptide synthesis and for the ELISA test. Reactivity was very intense with peptides n° 43, 44, 45, 46, 47 corresponding to: peptide 43 SQPPTRPPSRLRP SEQ ID NO: 160 peptide 44 PPTRPPSRLRPLG SEQ ID NO: 161 peptide 45 TRPPSRLRPLGAL SEQ ID NO: 162 peptide 46 PPSRLRP GALPA SEQ ID NO: 163 peptide 47 SRLRP GALPAPP SEQ ID NO: 164 The common sequence is SRLRP (SEQ ID NO : 165 ) . Positive reactivity has been obtained with peptides n° 34, 35, 36, 37, 38 corresponding to: peptide 34 NIATRFNYLPTAN SEQ ID NO : 166 peptide 35 ATRFNYLPTANPP SEQ ID NO 167 peptide 36 RFNYLPTANPPVG SEQ ID NO 168 peptide 37 NYLPTANPPVGPS SEQ ID NO 169 peptide 38 LPTANPPVGPSQP SEQ ID NO 170 The common sequence is LPTAN (SEQ ID NO : 171 ) . The major epitopes of SENV-D are, therefore, SRLRP (SEQ ID NO : 165 ) and LPTAN (SEQ ID NO : 171 ) . Example 31 Development of a SENV-C and SENV-E specific PCR and screening of clinical samples Given the clinical implications of the different SENV subtypes, a method for selectively amplifying and detecting SENV-C and SENV-E was developed. First, all the available SENV sequences were aligned and specific primers and a specific probe for SENV-C and SENV-E were identified. DNA extracted from 5 patients infected with SENV-A, 5 with SENV-B, 5 with SENV- C, 5 with SENV-D and 5 with SENV-E was amplified by PCR with primers SENV-C 5S (SEQ ID NO: 172) and primer L 2AS (SEQ ID NO: 71). The PCR reactions were performed as described herein above and consisted of a preheating at 94°C for 5 min, 40 cycles of 94°C for 1 min, 62 °C for 1 min, and 72°C for 1 min, and an incubation at 72°C for 7 min. In order to verify the specificity of the amplified products, aliquots of 5 ul of each amplified products were hybridized in a DEIA assay with the biotinilated probe NEW C Biot (SEQ ID NO: 173) internal to the amplicons. Only the 5 SENV-C patient samples gave positive results, all the other samples were negative. This demonstrated that the PCR method selectively amplifies SENV-C sequences. Additionally, DNA extracted from 5 patients infected with SENV-A, 5 with SENV-B, 5 with SENV-C, 5 with SENV-D and 5 with SENV-E was amplified by PCR with primers EK2S (SEQ ID NO: 174) and primer EK4AS (SEQ ID NO: 175). The PCR reactions were again performed as described herein above and consisted of a preheating at 94°C for 5 min, 40 cycles of 94°C for 1 min, 55 °C for 1 min, and 72°C for 1 min, and an incubation at 72°C for 7 min. In order to verify the specificity of the amplified products, aliquots of 5 ul of each amplified products were hybridized in a DEIA assay with the biotinilated probe NEW E Biot (SEQ ID NO: 176) internal to the amplicons. Only the 5 SENV-E patient samples gave positive results, whereas all the other samples were negative. This demonstrated that the method selectively amplifies SENV-E sequences. This methology for specifically detecting SENV subtypes allowed the screening of specific patient samples in order to elucidate which SENV subtypes are specifically involved in transmitting hepatitis, especially NANE hepatitis. Thus, highly selected sera were tested for the presence of the SENV family as well as for the presence of each individual subtype using the methods described herein above. Figure 62 A shows the percentage of positive samples among healthy blood donors (60 Italians and your 20 US citizens), HIV+ intravenous drug users (IVDU) and thalassemic patients. These data show that SEN viruses can be transmitted through blood, however big differences exist among the different subtypes. SENV-B, for instance, is highly prevalent in the healthy population and this suggests that it may not be pathogenic. SENV-A is highly prevalent in IVDU and less in thalassemic patients. Without being bound by theory, one possible interpretation for the unusual distribution of SENV-A is that it may be more resistant to atmospheric agents than the other SENV subtypes. Figure 62 B compares the SENVs prevalence among patients affected by alcoholic hepatitis, patients with chronic NANE hepatitis from US and patients with chronic NANE hepatitis from Japan. These data show that SENV-C and SENV-D may be responsible for at least some chronic NANE hepatitis in US. Interestingly, the SENV-C subtype appears to be completely absent in Japanese patients. However, in these Japanese patients, a large predominance of SENV-D can be detected. One of the Japanese patients was also co-infected with SENV-A. Figure 62 C compares the prevalence of SENVs among patients that had heart surgery without transfusions, patients that had heart surgery with transfusions and did not developed hepatitis and patients that developed hepatitis after one single transfusion. The data clearly demonstrate that SENV-C and SENV-D are related to post- transfusional hepatitis transmission. Taken together, these data also show that the family of SEN viruses is highly heterogeneous not only in terms of structural diversity but also in terms of biological effects. SENV-D and SENV-C appear to be associated to hepatitis transmission while the other subtypes do not play any role in this pathology. In particular SENV-B appears to be quite prevalent in the normal population. Without being bound by theory, this suggests that SENV-B may not have a pathogenic role. In order to further establish the role of SENV-C and SENV-D in hepatitis transfusion numerous control sera obtained from patients suffering from a plurality of diseases were tested. Figure 63 shows the results obtained with 486 samples. The data show the cumulative percentage of sera positive for SENV-C or SENV-D. SENV-D and SENV-C were selectively found in a high percentage of NANE-hepatitis patients but not in patients affected by other diseases. The two viruses were also found in a low but significative percentages of patients infected with hepatitis C or hepatitis B, suggesting that the route of transmission of SENV-C and SENV-D is similar to the one of other hepatitis viruses. SEQ ID NO: 177 relates to the prevalent SENV-C sequence obtained with primers C5S (SEQ ID NO: 172) and 2AS (SEQ ID NO: 71) which was detected in the sera of NANE patients and shows high similarity to the above-described SENV-C sequence (SEQ ID NO: 75). Although this sequence is similar to SENV-C, several mismatches have been identified with the canonic sequence and therefore its relation to SENV-C remains at this point only speculative. Example 32 Identification of SENV-F, SENV-G and SENV-H In order to study whether SENV viruses can also be found in lymphocytes PCR reactions on DNA extracted from purified lymphocytes were performed. These lymphocytes were obtained from 4 patients which were intravenous drug users and HIV positive. These patients were identified as VIR 18, VIR 16, VIR 12 and VIR 10. Their sera were SENV positive. For PCR reactions, primer NEW BCD 1 S (SEQ ID NO: 115) was used in combination with primer L 2AS (SEQ ID NO: 71). The PCR reactions were performed on 1 μg of isolated lymphocyte DNA which was deluted in a 50 μl PCR reaction mixture as described before (see, inter alia, example 9). The PCR reaction was performed in a DNA thermal cycler with mineral oil and consisted of a preheating at 94°C for 5 min, 40 cycles of 94°C for 1 min, 54°C for 1 min, and 72°C for 1 min, and an incubation at 72°C for 7 min. In order to test the specificity of the amplified products, aliquots of 5 μ! of each amplified product were hybridized in the previously described DEIA assay with the a SENV-specific probe (SEQ ID NO: 98) specific for a conserved sequence. All the four samples were positive, suggesting that human peripheral blood cell (PBL) can indeed harbor SEN viruses. In order to identify the SENV subtypes present in these samples, the isolated PBL DNAs were studied using the method described in examples 20 and 31. The presence of SENV-B was analized using the method described in example 17. VIR 18, VIR 16 and VIR 12 resulted positive for SENV-A, SENVD and SENV-C respectively. However, VIR 10 resulted negative for the presence of all known SENV subtypes, suggesting the presence of a new viral isolate. In order to obtain the complete sequence of this new SEN virus two different PCR reactions were set up. First, primers L 2AS ( SEQ ID NO: 71) and TTV15S (SEQ ID NO: 72) were used which were derived from the available sequence of SENV-D (SEQ ID NO: 53) and from the most 5' region of the TTV sequence. In the second reaction primers NEW BCD 1 S (SEQ ID NO: 115) and primer 662AS (SEQ ID NO: 86) were used. The PCR reactions were performed with a 50-μl mixture containing template, as described herein above. It was performed in a DNA thermal cycler with mineral oil and consisted of a preheating at 94°C for 5 min, 45 cycles of 94°C for 1 min, 58°C for 1 min, and 72°C for 1 min, and an incubation at 72°C for 7 min. Using this strategy, amplicons of about 1350 and 1614 bp were obtained. Gel pieces corresponding to the amplified bands were cut out, extracted and the extracts were connected to a pGEM vector (Promega, Madison, WI, USA), further introduced into E. coli. The DNA sequences of the inserts were determined as described herein above. Several clones that overlapped in the 5' and 3' regions were obtained and asembled employing the ASSEMLGEL program. Three unique sequence of about 3340 bases encoding for most, if not all of three new SENV genomes were obtained. The first sequence was named SENV-F (SEQ ID NO: 179). SENV-F contains three open reading frames (ORF1 , ORF 2 and ORF 3) respectively of 758, 160 and 182 amino acids (SEQ ID NO: 180, SEQ ID NO: 181 and SEQ ID NO: 182). Surprisingly, the ORF 3 of SEN-F is much longer (185 amino acid) than the one of the other SENVs which, containing only 80 amino acid in average. This is due to the presence of a methionine upstream to the two consecutive methionines present in all the other isolates. The percentage of identity of these proteins with those of the other SENVs and of TTV is shown in Figure 64. At the nucleotide level the identities of the entire genome of SENV-F with the one of SENV-A, B, C, D, E and TTV are 66.23, 62.54, 63.54, 75.21 , 61.66 and 56.59. The identities of the nucleotide sequences encoding for SENV-F ORF1 , ORF2 and ORF3 (SEQ ID NO: 183, SEQ ID NO: 184 and SEQ ID NO: 185) with the homologous regions of SENV-A, B, C, D, E, F and TTV are shown in Fig 65. Finally, the identity of the entire SENV-F nucleotide coding region (SEQ ID NO: 186) with the corresponding region of TTV was found to be 45,92%. Collectively, these data show that SENV-F is an additional member of the SENV family and, within this family, it appears closely related to SENV-D. The second sequence was named SENV-G (SEQ ID NO 187). As all the other SEN viruses , SENV-G contains three open reading frames (ORF1 , ORF 2 and ORF 3), respectively, comprising 763, 146 and 82 amino acids (SEQ ID NO: 188, SEQ ID NO: 189 and SEQ ID NO: 190). The percentage of identity of these proteins with those of the other SENVs and of TTV is shown in Figure 64. At the nucleotide level the identities of the entire genome of SENV-G with the one of SENV-A, B, C, D, E, F and TTV are 66.23, 62.54, 63.54, 75.21 , 61.66 and 56.59 while the identity between the coding region of SENV-G (SEQ ID NO: 191 ) and the coding region of TTV is 43,27%. The identities of the nucleotide sequences encoding for SENV-G ORF1 , ORF2 and ORF3 (SEQ ID NO: 192, SEQ ID NO: 193 and SEQ ID NO: 194) with the homologous regions of SENV- A, B, C, D, E, F and TTV are shown in Fig 65. Collectively these data establish that SENV-G is an additional member of the SENV family and, within this family, it appears to be equally distant with all the other SENV members. The third sequence was named SENV-H (SEQ ID NO 195). SENV-H contains three open reading frames (ORF1 , ORF 2 and ORF 3) of 762, 156 and 87 amino acids (SEQ ID NO: 196, SEQ ID NO: 197 and SEQ ID NO: 198), respectively. The percentage of identity of these proteins with those of the other SENVs and of TTV is shown in Figure 64. At the nucleotide level the identities of the entire genome of SENV-H with the one of SENV-A, B, C, D, E, F, G and TTV are respectively 63.77%, 59.87%, 81.03%, 60.89%, 58.88%, 59.72%, 62.00% and 53.50%; while the identity between the coding region of SENV-H (SEQ ID NO: 199) with the coding region of TTV is 48.97%. The identities of the nucleotide sequences encoding for SENV-H ORF1 , ORF2 and ORF3 (SEQ ID NO: 200, SEQ ID NO: 201 and SEQ ID NO: 202) with the homologous regions of SENV-A, B, C, D, E, F, G and TTV are shown in Fig 65. These data show that SENV-H is an additional member of the SENV family and, within this family, it appears to be closely related to SENV-C. EXAMPLE 33 PERSISTENCE OF SENV VIREMIA In order to elucidate whether SENV viremia is transient or can persist over time one HIV patient that registered for Higly Active Antiretroviral Therapy (HAART) was selected and serum samples were collected at the time of the HAART entry and 4, 8, 16, 24, 30, 32 and 40 weeks later. HIV viremia was monitored by an Amplicore HIV quantitative test (Roche Diagnostics) while SENV viremia was monitored by a PCR assay using primers NEW BCD 1S (SEQ ID NO: 115 in combination with primer L 2AS (SEQ ID NO: 71). The PCR reactions were performed with a 50-μl mixture containing template comparison, 1/10 th of DNA extracted from 100 ul of serum from said patient employing PCR conditions as described herein above. The reaction was performed in a DNA thermal cycler with mineral oil and consisted of a preheating at 94°C for 5 min, 40 cycles of 94°C for 1 min, 54°C for 1 min, and 72°C for 1 min, and an incubation at 72°C for 7 min. In order to verify the specificity of the amplified products, aliquots of 5 ul of each amplified products were hybridized in a DEIA assay with a SENV-specific probe (SEQ ID NO: 98) .specific for a conserved sequence. The result of these studies are shown in Fig. 66. HIV viremia was extremely high at the time of entry, however, already at 4 weeks after the beginning of HAART it started to decrease dramatically and continued to progressively decrease until it became almost undetectable by week 24. In contrast, SENV viremia was also very high at the time of entry but it was not affected by the HAART treatment. Thus, SENV can induce a persistent infection possibly leading to a chronic state. Furthermore, the results demonstrate that SENV is not sensible to HIV therapy. EXAMPLE 34 Detection of SENV in peripheral blood lymphocytes Peripheral Blood Cells were isolated from of 4 SENV positive and 4 SENV negative patients by Ficoll density gradient. After the isolation the cells, they were repeatedly washed and the DNA from 2 x 10 6 cells was isolated using a QIAamp DNA Blood kit (QIAGEN). The presence of SENV was monitored a PCR assay using primers NEW BCD 1S (SEQ ID NO: 115) in combination with primer L 2AS (SEQ ID NO: 71). The PCR reactions were performed as described in example 31 , i.e. 1 μg of starting DNA obtained as described herein above was diluted in 50 μl PCR reaction buffer. The reaction was performed in a DNA thermal cycler with mineral oil and consisted of a preheating at 94°C for 5 min, 40 cycles of 94°C for 1 min, 54°C for 1 min, and 72°C for 1 min, and an incubation at 72°C for 7 min. In order to verify the specificity of the amplified products, aliquots of 5 μl of each amplified products were hybridized in a DEIA assay with the a SENV-specific probe (SEQ ID NO: 98) specific for a conserved sequence. Results shown in Figure 67 demonstrate that the peripheral blood lymphocytes of the SENV positive patients, harbored the virus. The possibility that the virus detected in these cells is due to a residual blood contaminant is very unlikely since the cells have been extensively washed. Example 35 Culturing SENV in vitro The presence of SENV in peripheral blood cells rose the interesting possibility of culturing the virus in vitro. To study this possibility and to exclude the possibility that the presence of the virus in peripheral blood cells was simply due to passive attachement of the virus on cell membranes, peripheral blood cells were isolated from a SENV positive patients as described in example 34. Cells were cultured 5 ml at a staring density of 0.5 x 10 6 /ml of RPMI 1640 medium (Life technologies) supplemented with 10% fetal calf serum (FCS), in the presence of 1 μg/ml of Phytoagglutinin (PHA). Two hundred microliters of supernatant were carefully removed at days 1 , 2, 3, 4 and 5 of culturing. DNA was extracted from the centrifuged supernatants aliquots and amplified using primers NEW BCD 1 S (SEQ ID NO: 1 15) in combination with primer L 2AS (SEQ ID NO: 71). The PCR reactions were performed as described herein above. It was performed in a DNA thermal cycler with mineral oil and consisted of a preheating at 94°C for 5 min, 40 cycles of 94°C for 1 min, 54°C for 1 min, and 72°C for 1 min, and an incubation at 72°C for 7 min. In order to verify the specificity of the amplified products, aliquots of 5 μl of each amplified products were hybridized in a DEIA assay with the a SENV-specific probe (SEQ ID NO: 98) specific for a conserved sequence. Figure 68 shows that already at day 1 of culturing the SENV virus was detectable in the cell supernatant but, more important, the level of the virus increased constantly in the supernatant during the following three days of culture. The decrease of the virus level observed in the supernatant of day 5 of culture reflect, probably, the effect of dead cells and the subsequent release of protease and DNase. In conclusion, these experiments demonstrate that the virus can be obtained in vitro by culturing cells from infected individuals. This rises the possibility of obtaining large quantities of virions that can be used as source of viral antigens. EXAMPLE 36 Detection of SENV RNA in liver tissue In order to study whether SEN virus can replicate in the liver, two SENV positive patients were selected, who underwent surgery due to liver carcinomas. RNA was extracted from 25 mg tissue obtained from a peritumoral region and organ transformed liver tissue using the S.N.A.P. TM Total RNA isolation Kit (Invitrogen) according to a slight modification of the manufacturer instructions. The modification consisted of incubating eluted nucleic acids with Rnase-free Dnase for 30 minutes at 37 ° instead of the 10 minutes incubation suggested by the manufacturer. The eluted RNAs (125 μl) were precipitated with 2 volumes of ethanol and 1/10 th volume of sodium acetate pH 5.2, 3 M for 1 hour at - 20°C. The pelleted RNA was washed with 500 ul of 75% ethanol, centrifuged and resuspended in 25 ul of Rnase- free water. Ten μl of RNA were retrotrascribed to single stranded DNA using the SUPERSCRIPT ™ II Rnase H ' reverse transcriptase (Gibco BRL) using 500 ng of primer L3AS (SEQ ID 42) in a final volume of 20 ul. Five ul of cDNA and 2.5 ul of RNA (as control) were amplified using primers NEW BCD 1S (SEQ ID NO: 115) in combination with primer L 2AS (SEQ ID NO: 71). The PCR reactions were performed on 4 μl isolated cDNA whcih was diluted into 50 ml PCR-reaction buffer as described herein above. The PCR reaction was performed in a DNA thermal cycler with mineral oil and consisted of a preheating at 94°C for 5 min, 40 cycles of 94°C for 1 min, 54°C for 1 min, and 72°C for 1 min, and an incubation at 72°C for 7 min. In order to verify the specificity of the amplified products, aliquots of 5 ul of each amplified products were hybridized in a DEIA assay with the a SENV-specific probe (SEQ ID NO: 98) specific for a conserved sequence. Figure 69 shows that all the cDNAs, but not the RNA could be specifically amplified with SENV primers, demonstrating that SEN virus can replicate in the liver, since DNA viruses must have an RNA intermediate during replication. Example 37 Deposit of SENV-sequences at the DSMZ, Braunschweig, Germany Plasmids containing inserts corresponding to the SENV sequences have been deposited at the Deutsche Sammlung von Mikroorganismen und Zellkulturen (DSMZ) GmbH (German Collection of Microorganisms and Cell Cultures), Mascheroder Weg 1 b, D-38124 Braunschweig, GERMANY. The deposition was carried out in accordance with the Budapest Treaty on July 28, 1999 (DSM 12941 , DSM 12942, DSM 12943, DSM 12944, DSM 12957, DSM 12945, DSM 12958, DSM 12946, DSM 12947, DSM 12950, DSM 12951 , DSM 12952, DSM 12953, DSM 12959, DSM 12954) and on October 13, 1999 (DSM 13092, DSM 13093, DSM 13094 DSM 13095, DSM 13096, DSM 13097, DSM 13098). Duplicates of 22 "stubs" (solidified agar, containing the bacterial colony in a glass tube) comprising E. Coli bacteria XL1-blue (Sup E + , Lac " , hsdR17, recA1 , F'proAB, Lac l a , Lac ZAM 1 s) transformed with pGEM-Teasy vector or in E. Coli TOP 10 transformed with pCR R 2.1 -TOPO vector, TOPO TA Cloning kit (Invitrogen, Carlsbad, CA, USA) containing the different inserts (representing partial sequences of the different SENV subtypes) were deposited. The following stubs were deposited: SENV-A: A1 (Deposit number: DSM 12941 ): The insert is a 527bp fragment of SEQ ID NO: 24 from base 1813 to base 2340 A2 (Deposit number: DSM 12942): The insert is a 1082 bp fragment corresponding to the most 5' sequence of SEQ ID NO: 24 (from base 1 to base 1082) A3 (Deposit number: DSM 12943): The insert is a 1136 bp fragment corresponding to the most 3' sequence of SEQ ID NO: 24 (from base 2215 to base 3350) A4 (Deposit number: DSM 12944): The insert is a 1353bp fragment spanning base 1008 to base 2340 of SEQ ID NO: 24 A5 (Deposit number: DSM 12957): The insert is a 2196 bp fragment of SEQ ID 24 spanning base 850 to base3046, containing the entire sequence encoding for ORF1 SENV-B: B1 (Deposit number: DSM 12945): The insert is a 1798bp fragment corresponding to the most 5' sequence of SEQ ID NO: 34 (from base 1 to base 1798) B2 (Deposit number: DSM 12958): The insert is a 1563bp fragment corresponding to the most 3' sequence of SEQ ID NO: 34 (from base 2056 to base 3619) B3 (Deposit number: DSM 12946): The insert is a 1148bp fragment spanning base 1042 to base 2190 of SEQ ID NO: 34 SENV-C: C1 (Deposit number: DSM 12947): The insert is a 1536bp fragment corresponding to the most 5' sequence of SEQ ID NO: 75 (from base 1 to base 1536) C4 (Deposit number: DSM 13092): The insert is a 2285.bp fragment spanning base 576 to base 2861 of SEQ ID NO: 75 and containing the entire sequence encoding for ORF 1 SENV-D: D1 (Deposit number: DSM 12950): The insert is a 1798bp fragment corresponding to the most 5'sequence of of SEQ ID NO: 87 (from base 1 to base 1798) D2 (Deposit number: DSM 12951 ): The insert is a 1714bp fragment corresponding to the most 3' sequence of of SEQ ID NO: 87 (from base 1550 to base 3264) D3 (Deposit number: DSM 12952): The insert is a 2262bp fragment spanning base 584 to base 2846 of SEQ ID NO: 87 and containing the entire sequence encoding for ORF 1. SENV-E: E1 (Deposit number: DSM 12953): The insert is a 890bp fragment corresponding to the most 5'sequence of SEQ ID NO: 118 (from base 175 to base 1065) E2 (Deposit number: DSM 12959): The insert is a 2231 bp fragment corresponding to the most 3' sequence of SEQ ID NO: 118 (from base 1042 to base 3273) E3 (Deposit number: DSM 12954): The insert is a 1358bp fragment corresponding to the most 5' sequence of SEQ ID NO: 118 (from base 1 to base 1358) SENV-F: F1 (Deposit number: DSM 13093): The insert is a 1565bp fragment corresponding to the most 5'sequence of SEQ ID NO: 179 (from base 1 to base 1565) F3 (Deposit number: DSM 13094): The insert is a 2054bp fragment corresponding to the most 3' sequence of SEQ ID NO: 179 (from base 1286 to base 3340) SENV-G: G2 (Deposit number: DSM 13095): The insert is a 1453bp fragment corresponding to the most 5'sequence of SEQ ID NO: 187 (from base 1 to base 1453) G3 (Deposit number: DSM 13096): The insert is a 1936bp fragment corresponding to the most 3' sequence of SEQ ID NO: 187 (from base 1313 to base 3249) SENV-H: H2 (Deposit number: DSM 13097): The insert is a 1439bp fragment corresponding to the most 5'sequence of SEQ ID NO: 195 (from base 1 to base 1439) H1 (Deposit number: DSM 13098): The insert is a 1957bp corresponding to the most 3' sequence of SEQ ID NO: 195 (from base 1275 to base 3232) Maps of all deposited clones are shown in Figure 70. Example 38 Development of a SENV-G specific PCR A method for selective amplification of and detection for SENV-G was developed. To this end, all the available SENV sequences were aligned and primers and probe(s) which are potentially specific for SENV-G were identified. DNA extracted from 5 patients infected with SENV-A, 5 with SENV-B, 5 with SENV- C, 5 with SENV-D and 5 with SENV-E and 1 with SENV-G were amplified by PCR employing the primers VIR 17-1S (SEQ ID NO: 203) and primer SENVG-4AS (SEQ ID NO: 204). The PCR reactions on DNA extracted from serum in a PCR reaction mixture as described herein above and were performed in a DNA thermal cycler with mineral oil. This PCR consisted of a preheating at 94°C for 5 min, 40 cycles of 94°C for 1 min, 60 °C for 1 min, and 72°C for 1 min, and an incubation at 72°C for 7 min. In order to verify the specificity of the amplified products, aliquots of 5 μl of each amplified product were hybridized in the above described DEIA assay employing a specific , biotinylated probe "G-Biot" (SEQ ID NO: 205). Only one sample (patient infected with SENV-G) resulted positive employing this probes. All the other samples were negative, demonstrating that the method selectively amplifies SENV-G sequences. 3LDAPEST TREAT ON ThΞ INTERNATIONAL -COGMΗON OF THE DEPOSIT OF MICROO' C -vNISMS FOR THE PURPOSES Or PATENT PROCEDURE 117 INTERNATIONAL FORM Diasorin S.R.L Centro Ricercr.e Biomolecolaπ Via Calatafirrα M 1 1-25122 Brescia ECEIPT ΓN THE CASE OF AN ORIGI L DEPOSIT issued pursuant to Rule 7 1 by the INTERNATION AL DEPOSITARY AUTHORITY identified at the bottom of this page I IDENTIFICATION OF THE MICROORGANISM Identification reference given bv the DEPOSITOR AcceiS.on numDer given by the INTERNAT IO AL DEPOSITARY AUTHORITY Al DSM 12941 II SCIENTIFIC DESCRIPTION AND/OR PROPOSED TAXONOMIC DESIGNATION The microorganism identified under I above was accompanied by (X ) a scientific description (X ) a proposed taxonomic designation (Mark with a cross where applicable) III RECEIPT AND ACCEPTANCE This International Depositary Authorir. accepts the microorganism identified under I above which was received by it on 1 9 9 9 - 07 - 2 Ϊ (Date of the original deposit)' IV RECEIPT OF REQUEST FOR CONVERSION The microorganism identified under I above wa^ received bv this International Deposuan Authority on (date of original deposit) and a request to convert the original deposit to a deposit under the Budapest Treatv was received by it on (date of recs pt of request for conversion) V INTERNATIONAL DEPOSITAR AUTHORITY Name DSMZ-DEUTSCHE SAMMLUNG VON Sιgnature(s) of person(s) having the power to represent the MIKROORGANISMEN UND ZELLKULTUREN GmbH liuε ' natioπal Depositary Authorir, or of authorized officιal(s) Address Mascheroder Weg l b D-38l 2 4 Braunschweig us^' ~ L Ό Date 1999 - C S - 02 1 Where Rule 64 (d) applies such date is the date on which the sums ot international depositary authority was acquired Form DSMZ-BP/4 (sole page) 0196 BUDAPEST TREATY ON THE INTERNATION AL -COGNITION OF THE DEPOSIT OF MICROORGANISMS FOR ThE PURPOSES OF PATENT PROCEDURE 118 INTERNATIO AL FORM Diasoπn S.R.L. Centro Ricerche Biomolecolan Via Calatafimi N.l 1-25122 Brescia RECEIPT IN THE CASE OF AN ORIGINAL DEPOSIT issued pursuant to Rule 7 I bv the INTERNATIONAL DEPOSITARY AUTHORITY identified at the bottom ot this page 1 IDENTIFICATION OF THE MICROORGANISM Identification reference given bv the DEPOSITOR Accession number given bv the INTERNATIONAL DEPOSITARY AUTHORITY A2 DSM 12942 II SCIENTIFIC DESCRIPTION AND/OR PROPOSED TAXONOMIC DESIGNATION The microorganism identified under I above was accompanied by (X ) a scientific description (X ) a proposed taxonomic designation (Mark with a cross where applicable) III RECEIPT AND ACCEPTANCE This International Depositary Authority accepts the microorganism identified under I above, which was received by it on 1999 - 07 - 28 (Date of the original deposit)' IV RECEIPT OF REQUEST FOR CONV ERSION The microorganism identified under I above was received bv tins International Depositary Authoritv on (date of original deposit) and a request to convert the original deposit to a deposit under the Budapest Treatv was received bv it on (date of receipt of request for conversion) V INTERNATIONAL DEPOSITARY AUTHORITY Name DSMZ-DEUTSCHE SAMMLUNG VON Sιgnature(s) ot person(s) having the power to represent the MIKROORGANISMEN UND ZELLKULTUREN GmbH International Depositary Authority or ot authorized Address Mascheroder Weg lb D-38 I24 Braunscnweia Date 1999 - 08 - 02 1 Where Rule 64 (d) applies, such date is the date on wnich the status ot international depositary aut ority was acquired Form DSMZ-BP/4 (sole page) 0196 BUDAPEST TREATY ON THE INTER ATION L ..COGNITION OF THE DEPOSIT OF MICROORGANISMS FOR THE PURPOSES OF PATENT PROCEDURE 119 INTERNATIONAL FORM Diasorin S.R.L. Centre Ricerche B omolecolaπ Via Calatafimi N. 1-25122 Brescia RECEIPT IN THE CASE OF AN ORIGINAL DEPOSIT issued pursuant to Rule 7 1 by the INTERNATIONAL DEPOSITARY AUTHORITY identified at the bottom of this page I IDENTIFICATION OF THE MICROORGANISM Identification reterence given by the DEPOSITOR Accession number given bv the INTERNATIONAL DEPOSITARY AUTHORITY A3 DSM 12943 II SCIENTIFIC DESCRIPTION AND/OR PROPOSED TAXONOMIC DESIGNATION The microorganism identified under I above was accompanied by (X ) a scientific description (X ) a proposed taxonomic designation (Mark with a cross where applicable) III RECEIPT AND ACCEPTANCE This Intemationai Depositary Authority accepts the microorganism identified under I above, which was received by it on 19 9 9 - 0 7 - 2 ! (Date of the original deposit)' IV RECEIPT OF REQUEST FOR CONVERSION The microorganism identified under I above was received b\ this International Depositary Autliority on (date of original deposit) and a request to convert the original deposit to a deposit under the Budapest Treaty was received by it on (date of receipt of request for conversion) V INTERNATIONAL DEPOSITARY AUTHORITY Name DSMZ-DEUTSCHE SAMMLUNG VON Sιgnature(s) of person(s) having the power to represent the M1KROOR.GANIS. EN UND ZELLKULTUREN GmbH International Depositary Authority or of authorized offιcιal(s) Address Mascheroder Weg lb D-3SI24 Braunschweig c > Date 1999 - 08 - 02 1 Where Rule 64 (d) applies, such date is the date on which the status of international depositary authority was acquired Form DSMZ-BP/4 (sole page) 0196 BUDAPEST RE A TY ON' THE INTERN TIONAL iCOGNTTIO OF THE DEPOSIT OF MICROORGANISMS FOR THE PURPOSES OF PATENT PROCEDURE 120 INTERN ATIONAL FORM Diasonn S.R.L. Cencro Ricεrche B omolecolaπ Via Calatafimi N.l 1-25122 Brescia RECEIPT IN THE CASE OF AN ORIGINAL DEPOSIT issued pursuant to Rule 7 1 by the INTERNATIONAL DEPOSITARY AUTHORITY identified at the bottom of this page I IDENTIFICATION OF THE MICROORGANISM Identification reterence given bv the DEPOSITOR Accession number given bv the INTERNATIONAL DEPOSITARY AUTHORITY A4 DSM 12944 II SCIENTIFIC DESCRIPTION AND/OR PROPOSED TAXONOMIC DESIGNATION The microorganism identified under I above was accompanied by (X ) a scientific description (X ) a proposed taxonomic designation (Mark with a cross where applicable) III RECEIPT AND ACCEPTANCE This Intemationai Depositary Authority accepts the micoorganism identified under I above which was received bv it on 1 9 9 9 - 0 7 - 2 ! (Date of the original deposit)' IV RECEIPT OF REQUEST FOR CONVERSION The microorganism identified under I above was received bv this International Depositary Authoritv on (date of original deposit) and a request to convert the original deposit to a deposit under the Budapest Treaty was received by it on (date ot receipt of request for conversion) V INTERNATIONAL DEPOSITARY AUTHORITY Name DSMZ-DEUTSCHE SAMMLUNG VON Sιgnature(s) ot pεrsoπ(s) having the power to represent the MIKROORGANISMEN UND ZELLKULTUREN GmbH International Depositary Authority or of authorized officιal(s) Address Mascheroder Weg lb D-38124 Braunschweig Date 199 9 - 08 - 02 ' Where Rule 6 4 (d) applies, such date is the date on which die status of international depositary authority was acquired Form DSMZ-BP/4 (sole page) 0196 BUDAPEST TREATY' ON THE INTERNATIONAL -OGNITION OF THE DEPOSIT OF MICROORGANISMS FOR THE PURPOSES OF PATENT PROCEDURE 121 INTERNATIONAL FORM Diasorin S.R.L. Centre Ricerche Biomolecolari Via Calatafimi N.l 1-25122 Brescia RECEIPT IN THE CASE OF AN ORIGINAL DEPOSIT issued pursuant to Rule 7 1 by die INTERNATIONAL DEPOSITARY AUTHORITY identified at the bottom of tins page I IDENTIFICATION OF THE MICROORGANISM Identification reference given bv the DEPOSITOR Accession number given by the INTERNATIONAL DEPOSITARY AUTHORITY B l DSM 12945 II. SCIENTIFIC DESCRIPTION AND/OR PROPOSED TAXONOMIC DESIGNATION The microorganism identified under I. above was accompanied by (X ) a scientific description (X ) a proposed taxonomic designation (Mark with a cross where applicable) III. RECEIPT AND ACCEPTANCE This Intemationai Depositary Authority accepts die microorganism identified under I above, which was received by it on 1 9 9 S - 0 7 - 2 8 (Date of the original deposit)' IV RECEIPT OF REQUEST FOR CONVERSION The microorganism identified under I above was received by dns International Depositary Audiority on (date of original deposit) and a request to convert the original deposit to a deposit under the Budapest Treaty was received by it on (date of receipt of request for conversion) V INTERNATIONAL DEPOSITARY AUTHORITY Name DSMZ-DEUTSCHE SAMMLUNG VON Sιgnature(s) of person(s) having tne power :o represent the MIKROORGANISMEN UND ZELLKULTUREN GmbH International Depositary Authoritv or of authorized offιcιal(s) Address Mascheroder Weg l b D-38124 Braunschweig Date. 1999 - 08 - 02 ' Where Rule 6 4 (d) applies, such date is the date on which the status of international depositary authority was acquired Form DSMZ-BP/4 (sole page) 0196 BUDAPEST TREATY ON THE INTERNATIONAL .^COGNITION OF THE DEPOSIT OF MICROORGANISMS FOR THE PURPOSES OF PATENT PROCEDURE 122 INTERNATIONAL FORM Diasorin S.R.L. Centro Ricerchε Biorπolecolari Via Calatafimi N.l 1-25122 Brescia RECEIPT IN THE CASE OF AN ORIGINAL DEPOSIT issued pursuant to Rule 7 1 bv the INTERNATIONAL DEPOSITARY AUTHORITY identified at the bottom of this page I IDENTIFICATION OF THE MICROORGANISM Identification reference given by the DEPOSITOR Accession number given by the INTERNATIONAL DEPOSITARY AUTHORITY B3 DSM 12 946 II. SCIENTIFIC DESCRIPTION AND/OR PROPOSED TAXONOMIC DESIGNATION The microorganism identified under I. above was accompanied by: (X ) a scientific description (X ) a proposed taxonomic designation (Mark with a cross where applicable) III RECEIPT AND ACCEPTANCE This International Depositary Authority accepts the microorganism identified under I. above, which was received by it on 1 9 9 9 - 0 7 - 2 8 (Date of the original deposit)'. IV RECEIPT OF REQUEST FOR CONVERSION The microorganism identified under I above was received by this International Depositary Authority on (date of original deposit) and a request to convert the original deposit to a deposit under the Budapest Treaty was received by it on (date of receipt of request for conversion) V INTERNATIONAL DEPOSITARY AUTHORITY Name DSMZ-DEUTSCHE SAMMLUNG VON Sιgnature(s) of person(s) having the power to represent the MIKROORGANISMEN UND ZELLKULTUREN GmbH International Depositary Authority or of authorized otTιcιal(s) Address Mascheroder Weg lb D-38124 Braunschweig Date 1999 - 08 - 02 ' Where Rule 6 4 (d) applies, such date is the date on which die status of international depositary audiority was acquired. Form DSMZ-BP/4 (sole page) 0196 BUDAPEST TREATY ON THE INTERN ATIONAL JΞCOGNTΠON OF THE DEPOST OF MICROORGANISMS FOR THE PURPOSES OF PATENT PROCEDURE 123 INTERNATIONAL FORM Diasonn S.R.L. Centre Ricerche Biomolecolari Via Calatafimi N.l 1-25122 Brescia RECEIPT IN THE CASE OF AN ORIGINAL DEPOSIT issued pursuant to Rule 7 1 by the INTERNATIONAL DEPOSITARY AUTHORITY identified at the bottom of this page I. IDENTIFICATION OF THE MICROORGANISM Identification reference given by the DEPOSITOR Accession numoer given oy die INTERNATIONAL DEPOSITARY AUTHORITY Cl DSM 12947 II. SCIENTIFIC DESCRIPTION AND/OR PROPOSED TAXONOMIC DESIGNATION The microorganism identified under I. above was accompanied by (X ) a scientific description (X ) a proposed taxonomic designation (Mark with a cross where applicable) III RECEIPT AND ACCEPTANCE This International Depositary Authority accepts the microorganism identified under I aoove which was received by it on 1 9 9 9 - 0 7 - (Date of the original deposit)' IV RECEIPT OF REQUEST FOR CONVERSION The microorganism identified under I above was received bv this International Depositary Authority on (date of original deposit) and a request to convert the original deposit to a deposit under die Budapest Treaty was received by it on (date ot receipt of request for conversion) V. INTERNATIONAL DEPOSITARY AUTHORITY Name DSMZ-DEUTSCHE SAMMLUNG VON Sιgπature(s) of person(s) having the power to represent the MIKROORGANISMEN UNO ZELLKULTUREN GmbH International Depositary Authority or of authorized officιal(s) Address Mascheroder Weg lb D- S1 4 Braunschweig Date 1999 - 08 - 02 Where Rule 6 4 (d) applies, such date is the date on which die status of international depositary audiority was acquired Form DSMZ-BP/4 (sole page) 0196 3LDA D EST TREATY ON Tr INTERN ATION L. .RECOGNITION OF THE DEPOS T OF N1CROORGANISMS FOR THE PURPOSES OF PATENT P OCEDURE 124 INTERNATION AL FORM Diasoπn S.R.L. Centro Ricerchε Binraolecolari Via Calatafimi .l 1-25122 Brescia RECEIT ΓM THE CASE OF AN ORIGI AL DEPOSIT issued pursuant to Rule 7 1 bv the INTERNATIONAL DEPOSITARY AUTHORITY identified at die bottom of this page I IDENTIFICATION OF THE MICROORG NISM Identification reference given bv the DEPOSITOR Accession numoer given bv the INTERNATIONAL DEPOSITARY ALTHORITΛ Dl DSM 12950 II SCIENTIFIC DESCRIPTION AND/OR PROPOSED TAXONOMIC DESIGNATION The microorganism identified under I above was accompanied by (X ) a scientific description (X ) a proposed taxonomic designation (Mark with a cross where applicable) III RECEIPT AND ACCEPTANCE This International Depositary Authoritv accepts the microorganism identified undc I above which was received bv it on 19 9 9 - 0 / - 2 8 (Date of the original deposit)' IV RECEIPT OF REQUEST FOR CONVERSION The microorganism identified under I above was received bv this International Depositary Authority on (date of ong-nal deposit) and a request to convert the original deposit to a deposit under the Budapest Treatv was received bv it on (date ot receipt of request for conversion) V INTERNATIONAL DEPOSITARY AUTHORITY Name DSMZ-DEUTSCHE SAMMLUNG VON Sιgnature(s) ot person(s) having the power to represent the MIKROORGANISMEN UND ZELLKULTUREN GmbH l-,ternatιoπal Depositary Authority or of audioπzed officιal(s) Address Mascheroder Weg lb D-38124 Braunschweig Date 1999 - 08 - 02 ' Where Rule 64 (d) applies, such date is the date on which the status of international depositary authority was acquired BUDAPEST TREATY' ON THE INTERN TIO L -COGNITION OF THE DEPOSIT OF MICROORGANISMS FOR THE PURPOSES OF PATENT PROCEDURE 125 INTERNATIONAL FORM Diasorin S . R . L . Centre- Ricerche Biomolecolari Via Calataf irαi N . 1 - 25122 Brescia RECEIPT IN ' THE CASE OF AN ORIGINAL DEPOSIT issued pursuant to Rule 7 1 by the INTERNATIONAL DEPOSITARY AUTHORITY identified at the bottom of this page IDENTIFICATION OF THE MICROORGANISM Identification reference given by the DEPOSITOR Accession number given bv the INTERNATIONAL " DEPOSITARY AUTHORITY D2 DSM 12951 II SCIENTIFIC DESCRIPTION AND/OR PROPOSED TAXONOMIC DESIGNATION The microorganism identified under I above was accompanied by (X ) a scientific description (X ) a proposed taxonomic designation (Mark with a cross where applicable). HI RECEIPT AND ACCEPTANCE This Intemationai Depositary Authority accepts the microorganism identified under I above, which was received by it on 19 9 9 - 0 7 - 2 ! (Date of the original deposit)'. IV RECEIPT OF REQUEST FOR CONVERSION The microorganism identified under I above was received by this International Depositary Authoritv on (date of original deposit) and a request to convert the original deposit to a deposit under the Budapest Treaty was received bv it on (date of receipt of request for conversion) V INTERNATIONAL DEPOSITARY AUTHORITY Name DSMZ-DEUTSCHE SAMMLUNG VON Sιgπature(s) of person(s) ha ing the power to represent the MIKROORGANISMEN UND ZELLKULTUREN GmbH International Depositary Authority or of authorized offιcιal(s) Address Mascheroder Weg lb D-38124 Braunschweig Date. 1999 - 08 - 02 ' Where Rule 6 4 (d) applies, such date is the date on which the status of international depositary authority was acquired - P BUDAPEST TREATY ON THE INTER TIO L -OGNITION OF THE DEPOSIT OF MICROORGANISMS FOR THE PURPOSES OF PATENT PROCEDURE 126 INTERN TIONAL FORM Diasorm S.R. . Centro Ricerche Biomolecolari Via Calatafimi N.l 1-25122 Brescia RECEIPT IN THE CASE OF AN ORIGfNAL DEPOSIT issued pursuant to Rule 7 1 by the INTERNATIONAL DEPOSITARY AUTHORITY identified at the bottom of dns page I. IDENTIFICATION OF THE MICROORGANISM Identification reference given by the DEPOSITOR Accession nu.nber given by the INTERNATIONAL DEPOSITARY AUTHORITY D3 DSM 12952 II. SCIENTIFIC DESCRIPTION AND/OR PROPOSED TAXONOMIC DESIGNATION The microorganism identified under I above was accompanied by (X ) a scientific description (X ) a proposed taxonomic designation (Mark with a cross where applicable) III. RECEIPT AND ACCEPTANCE This Intemationai Depositary Authority accepts the microorganism identified under I above, which was received by it on 199 9 - 07 - 2 ! (Date of the original deposit)' IV. RECEIPT OF REQUEST FOR CONVERSION The microorganism identified under I above was received by this Intemationai Depositary Authority on (date of original deposit) and a request to convert the original deposit to a deposit under the Budapest Treatv was received by it on (date of receipt of request for conversion) V. INTERNATIONAL DEPOSITARY AUTHORITY Name DSMZ-DEUTSCHE SAMMLUNG VON Sιgπature(s) of person(s) having the power to represent the MIKROORGANISMEN UND ZELLKULTUREN GmbH International Depositary Audiority or of authorized officral(s) Address Mascheroder Weg lb D-38124 Braunschweig Date. 1999 - 08 - 02 1 Where Rule 6 4 (d) applies, such date is the date on wnich the status of international depositary authority was acquired Form DSMZ-BP/4 (sole pa e) 0196 BUDAPEST TREATY ON THE INTERNATIO L RECOGNITION OF THE DEPOSIT OF MICROORGANISMS FOR THE PURPOSES OF PATENT PROCEDURE 127 INTERNATIONAL FORM Diasoπn S.R.L. Centro Ricerche Biomolecolan Via Calatafimi N.l 1-25122 Brescia RECEIPT IN THE CASE OF AN ORIGIN AL DEPOSIT issued pursuant to Rule " " 1 by the INTERNATIONAL DEPOSITARY AUTHORITY identified at the bottom ot this page I IDENTIFICATION OF THE MICROORGANISM Identification reference given by the DEPOSITOR Accession number given bv the INTERNATIONAL " DEPOSITARY AUTHORITY' El DSM 12953 II SCIENTIFIC DESCRIPTION AND/OR PROPOSED TAXONOMIC DESIGNATION The microorganism identified under I above was accompanied by (X ) a scientific description (X ) a proposed taxonomic designation (Mark with a cross where applicable) III RECEIPT AND ACCEPTANCE This Intemationai Depositary Authoritv accepts the microorganism identified under I above which was received by it on 1 9 9 9 - 0 7 - 2 ! (Date of the original deposit) 1 IV RECEIPT OF REQUEST FOR CONVERSION The microorganism identified under I above was received by this Intemationai Depositary Authority on (date of original deposit) and a request to convert the original deposit to a deposit under the Budapest Treatv was received by it on (date of receipt of request for conversion) V INTERNATIONAL DEPOSITARY AUTHORITY Name DSMZ-DEUTSCHE SAMMLUNG VON Sιgnature(s) of pcson(s) having the power to represent the MIKROORGANISMEN UND ZELLKULTUREN GmbH International Depositary Authoritv or of authorized officιai(s) Address Mascheroder Weg lb D-3S I24 Braunschweig Date 1999 - 08 - 02 1 Where Rule 6 4 (d) applies, such date is the date on which the status of international depositary authoritv was acquired - JUDAPEST TREATY ON THE INTERNATIONAL RECOGNITION OF THE DEPOSIT OF MICROORGANISMS FOR THE PURPOSES OF PATENT PROCEDURE 128 INTERNATION AL FORM Diasorin S.R.L. Centro Ricerche Biomolecolari Via Calatafimi N. 1-25122 Brescia RECEIPT IN THE CASE OF AN ORIGINAL DEPOSIT issued pursuant to Rule 7 1 by the INTERNATIONAL DEPOSITARY AUTHORITY identified at the bottom of this p3ge I IDENTIFICATION OF THE MICROORGANISM Identification reference given by the DEPOSITOR Accession number given by the INTERNATIONAL DEPOSITARY AUTHORITY E3 DSM 12954 II SCIENTIFIC DESCRIPTION AND/OR PROPOSED TAXONOMIC DESIGNATION The microorganism identified under I. above was accompanied by (X ) a scientific description (X ) a proposed taxonomic designation (Mark with a cross where applicable) III RECEIPT AND ACCEPTANCE This International Depositary Authority accepts the microorganism idertified under 1 above, which was received bv it on 19 9 9 - 07 - 2 ! (Date of the original deposit)' IV RECEIPT OF REQUEST FOR CONVERSION The microorganism identified under I above was received by this International Depositary Authoritv on (date of original deposit) and a request to convert the original deposit to a deposit under die Budapest Treaty was received by it on (date of receipt ot request for conversion) V INTERNATIONAL DEPOSITARY AUTHORITY Name DSMZ-DEUTSCHE SAMMLUNG VON Sιgnature(s) of persoπ(s) having the power to represent the MIKROORGANISMEN UND ZELLKULTUREN GmbH International Depositary Authority or of authorized officιal(s) Address Mascheroder Weg lb D-38124 Braunschweig Date. 1999 - 08 - 02 ' Where Rule 6 4 (d) applies, such date is the date on which the status of international depositary authority was acquired BUDAPEST TREATY ' ON THE INTERN AT O AL -COGNITION OF THE DEPOSIT OF MICROORGANISMS FOR THE PURPOSES OF PATENT PROCEDURE 129 INTERNATIONAL FORM Diasoπn S . R . L . Centro Ricerche Bioraolecolari Via Calataf imi N . l 1 - 25122 Brescia RECEIPT IN' THE CASE OF AN ORIGINAL DEPOSIT issued pursuant to Rule 7 1 bv the INTERNATIONAL DEPOSITARY AUTHORITY identified at tne bottom of tins page I IDENTIFICATION OF THE MICROORGANISM Identification reference given by the DEPOSITOR Accession number given bv the INTERN \TIONAL DEPOSITARY AUTHORITY A5 DSM 12957 II SCIENTIFIC DESCRIPTION AND/OR PROPOSED TAXONOMIC DESIGNATION The microorganism identified under I above was accompanied by (X ) a scientific description (X ) a proposed taxonomic designation (Mark with a cross where applicable) III RECEIPT AND ACCEPTANCE This International Depositary Authoritv accepts the microorganism identified under I above, which was received bv it on 1 9 9 9 - 0 7 - 2 8 (Date of the original deposit)' IV RECEIPT OF REQUEST FOR CONVERSION The microorganism identified under I above was received by this International Depositary Authoritv on (date of original deposit) and a request to convert the original deposit to a deposit under the Budapest Treaty was received by it on (date of receipt of request for conversion) V INTERNATIONAL DEPOSITARY AUTHORITY Name DSMZ-DEUTSCHE SAMMLUNG VON Sιgnaturc(s) of person(s) having the power to represent the MIKROORGANISMEN UND ZELLKULTUREN GmbH International Depositary Authority or of authorized officιal(s) Address Mascheroder Weg lb D-38124 Braunschweig Date 1999 - 08 - 02 ' Where Rule 6 4 (d) applies, such date is the date on which the status of international depositary authority was acquired Form DSMZ-BP/4 (sole page) 0196 BUDAPEST TREATY' ON THE INTERNATIO L RECOGNITION OF THE DEPOSIT OF MICROORGANISMS FOR THE PURPOSES OF PATENT PROCEDURE 130 INTERNATIONAL FORM Diasorin S.R.L. Centro Ricerche Biomoiecolari Via Calatafimi N.l 1-25122 Brescia RECEIPT IN THE CASE or AN ORIGINAL DEPOSIT issued pursuant to Rule 7 I by the INTERNATIONAL DEPOSITARY AUTHORITY' identified at die bottom of dns page I IDENTIFICATION OF THE MICROORGANISM Identification reference given by the DEPOSITOR Accession number given os the INTERNATIONAL DEPOSITARY AUTHORITY B2 DSM 12958 II. SCIENTIFIC DESCRIPTION AND/OR PROPOSED TAXONOMIC DESIGNATION The microorganism identified under I. above was accompanied by (X ) a scientific description (X ) a proposed taxonomic designation (Mark with a cross where applicable) III. RECEIPT AND ACCEPTANCE This International Depositary Authority accepts the microorganism identified under I above, which was received by it on 19 9 9 - 0 7 - 2 ! (Date of the original deposit)' IV RECEIPT OF REQUEST FOR CONVERSION The microorganism identified under I above was received by this International Depositary Authority on (date of original deposit) and a request to convert the original deposit to a deposit under die Budapest Treaty was received by it on (date of receipt of request for conversion) V INTERNATIONAL DEPOSITARY AUTHORITY' Name. DSMZ-DEUTSCHE SAMMLUNG VON Sιgπature(s) of person(s) having the power to represent the MIKROORGANISMEN UND ZELLKULTUREN GmbH International Deoosύarv Authority or of authorized officιal(s) Address Mascheroder Weg lb D-38124 Braunschweig Date 1999 - 08 - 02 ' Where Rule 6 4 (d) applies, such date is the date on which the status of international depositary audiority was acquired - BUDAPEST TRE ATY' ON THE INTERNATION AL r- COGNITION OF THE DEPOSIT OF MICROORG ISMS FOR THE PURPOSES OF PATENT PROCEDURE 131 INTERN ATION AL FORM Diasonn S.R.L. Centre Ricerche Biomolecolan Via Calatafimi N.l 1-25122 Brescia RECEIPT IN THE CASE OF AN ORIGINAL DEPOSIT issued pursuant to Rule 7 1 bv tne INTERNATIONAL DEPOSITARY AUTHORITY identified at the bottom of this page ' Where Rule 6 4 (d) applies, such date is die date on which the status ot international depositary audiority was acquired - BUDAPEST TREATY ON T.-Ξ INTER ATIONAL RECOGNITION OF THE DSPOSiT OF MICROORGANISMS FOR THE PURPOSES OF P T ENT PROCEDURE 132 INTERNATIONAL FORM Diasoπn S.R.L. Cεntro Ricerche Biomolεcolaπ Vra"Calatafimi N. 1-25122 Brescia RECEIPT IN THE CASE OF AN ORIGINAL DEPOSIT issued pursuant to Rule 7 1 by the INTERNATIONAL DEPOSITARY AUTHORITY lαentified at the bottom of this page 1 IDENTIFICATION OF THE MICROORGANISM Identification reference given b> the DEPOSITOR Aι_cesiion number given by the 1NTERNA1 ION AL~ DEPOSITARY AUTHORITY C4 DSM 13092 U SCIENTIFIC DESCRIPTION AND/OR PROPOSED TAXONOMIC DESIGN TION' The microorganism identified under I above was accompanied by (X ) a sciertific description (X ) a proposed taxonomic designation (Mark idi a cross where applicable) III RECEIPT AND ACCEPTANCE This Intemationai Depositary Authority accepts the microorganism identified under I above wnich was received by it on 19 99 - 10 - 13 (Date of the original deposit)' IV RECEIPT OF REQUEST FOR CONVERSION The microorganism identified under I above was received bv this Internatioml Depositary Authoritv on (date ot original deposit) and a request to convert the original deposit to a deposit under the Budapest Treatv was re.eived by it on (date ot receipt ot reauest lor conversion) V INTERNATIONAL DEPOSITARY AUTHORITY Name DSMZ-DEUTSCHE SAMMLUNG VON Sιgnαture(s) ot person(s) hiving the power to represent the MIKROORGANISMEN UND ZELLKULTUREN GmbH international Depositary Audioπrv or ot authorized oftιcιal(s) Address Mascheroder Weg lb D-38124 Braunschweig Date 1999 - 10 - 18 ' Where Rule 64 (d) applies, such date is die date on which the status ot international depos.tary audiority was acquired Form DSMZ-BP/4 (sole a e 0196 3UDAPEST TREATY' ON THE INTERN ATIO AL -COGNITION OF THE DEPOSIT OF MICROORGANISMS FOR THE PURPOSES OF PATENT PROCEDURE 133 INTERNATIONAL FORM Diasorm S.R.L. Centro Ricεrche Biomolecolari Via Calatafimi N. 1-25122 Brescia RECEIPT IN THE CASE OF AN ORIGIN AL DEPOSIT nsued pursuant to Rule 7 1 by the INTERNATIONAL DEPOSITARY ALT'rORπ identif ed at die bottom ot tins page I IDENTIFICATION OF THE MICROORGANISM Identification reference given bv die DEPOSITOR Accession numoer given bv the INTERNATIONAL DEPOSITARY AUTHORITY FI DSM 13093 II SCIENTIFIC DESCRIPTION AND/OR PROPOSED TAXONOMIC DESIGNATION The microorganism identified under I above was accompanied bv (X ) a scientific description (X ) a proposed taxonomic designation (Mark with a cross where applicable) III RECEIPT AND ACCEPTANCE This International Depositary Authoritv accepts die microorganism ident'fied under I aoove which was received by it on 1 9 9 9 - 1 0 - 1 3 (Date of the original deposit)' IV RECEIPT OF REQUEST FOR CONVERSION The microorganism identified under I above was received bv this International Depositary Authority on (date of original deoos.t) and a request to convert the original deposit to a deposit under die Budapest Treatv was received by it on (date ot receipt of req-est for conversion) V INTERNATIONAL DEPOSITARY AUTHORITY Name DSMZ-DCUTSCHE SAMMLUNG VON Sιgnature(s) ot person(s) having the power to represent the MIKROORGANISMEN UND ZELLKULTLREN GmbH International Depositary Authority or ot auihorized olti-ial(-) Address Mascheroder Weg lb D-38124 Braunschweig Date 199 9 - 10 - 18 ' Where Rule 64 (d) applies, such date is the date on wnich die status of international depositary authority was acquired Form DSMZ-BP/4 (sole page) 0196 BU DAPEST TREATY ON THE INTERNATIO L -COGNITION OF THE DEPOSIT OF MICROORGANISMS FOR THF PURPOSES OF PATENT PROCEDURE 134 INTERNATIONAL FORM Diasonn S.R.L. Centro R cerche Bicir.oleco-.ari V a Calatafimi N, 1-25122 Brescia RECEIPT IN THE CASE OF AN ORIGINAL DEPOSIT issued pursuant to Ru'e 7 1 by the INTERNATIONAL DEPOSITARY AUTHORITY identified at U'e bottom ot this page I IDENTIFICATION OF THE MICROORGANISM Identiacat.oπ reference given by die DEPOSITOR Accession nu oe- given by the INTERNATION AL " DEPOSITARY AUTHORITY F3 DSM 13094 II SCIENTIFIC DESCRIPTION AND/OR PROPOSED TAXONOMIC DESIGNATION The microorganism identified under I above was accompanied by (X ) a scientific description (X ) a proposed taxonomic designation (Mark with a cross where applicable) III RECEIPT AND ACCEPTANCE Th'S International Depositary Authority accepts the microorganism identified under I above which as rece d bv it on 19 9 9 - 10 - 13 (Date ot the original deposit)' IV RECEIPT OF REQUEST FOR CONVERSION The microorganism identified under I above w as received by d'is International Depositarv Authority on (dite of original deposit) and a request to convert the original deposit to a deposit under the Budapest Treatv was received by it on (date ot receipt ot request for conversion) V INTERNATIONAL DEPOSITARY AUTHORITY Name DSMZ-DEUTSCHE SAMMLUNG VON Signatures) ot person(s) hav ing the power to reorese it tl e MIKROORGANISMEN UND ZELLKULTUREN GmbH International D-positarv Authority or ot authorized otiiciaih) Address Mascheroder Weg lb D-38124 Braunschweig Date 199 9 - 10 - 1 ! ' Where Rule 6 4 (d) applies, such date is die date on which the status of international depositarv authoritv was acquired Form DSMZ-BP/4 (sole page) 0196 BUDAPEST TREATY ON THE INTERN ATO L ,OGNITiON OF THE DEPOSIT OF MICROORG ANISMS FOR THE PURPOSES OF PATENT PROCEDURE 135 INTERNATIONAL FORM Diasorin S.R.L. Cenr.ro Ricεrche Biomolecolari Via Calatafimi N. 1 1-25122 Brescia RECEIPT IN THE CASE OF AN ORIGINAL DEPOSIT issued pursuant to Rule 7 1 by the INTERNATIONAL DEPOSITARY AUTHORITY' identified at me bottom of this page I IDENTIFICATION OF THE MICROORGANISM dentificatioπ reference given by the DEPOSITOR Accession number given by the INTERNATIONAL " DEPOSITARY AUTHORITY G2 DSM 13 095 II. SCIENTIFIC DESCRIPTION AND/OR PROPOSED TAXONOMIC DESIGNATION The microorganism identified under 1 above was accompanied by (X ) a scientific description (X ) a proposed taxonomic designation (Mark with a cross where applicable) III. RECEIPT AND ACCEPTANCE This International Depositary Authority accepts die microorganism identified under I aaove, w hich was received bv it on 1 9 9 9 - 1 0 - 13 (Date of the original deposit)' IV. RECEIPT OF REQUEST FOR CONVERSION The microorganism identified under I above was received bv t is Intemationai Depositary Authority on (date ot original deposit) and a request to convert the original deposit to a deposit under the Budapest Treaty was received by it on (date of receipt ot request for conversion) V. INTERNATIONAL DEPOSITARY AUTHORITY Name DSMZ-DEUTSCHE SAMMLUNG VON Sιguature(s) ot pe.--on(s) having the power to represent the MIKROORGANISMEN UND ZELLKULTUREN GmbH International Depositary Authority or of authorized Address Mascheroder eg lb D-38124 Braunschweig Date 1999 - 10 - 18 1 Where Rule 6 4 (d) applies, such date is die date on wnich die status ot international depositary authority was acquired Form DSMZ-BP/4 (sole page) 0196 BUDAPEST TREATY ON ThE INTER TIONAL -OGNITION OF THE DEPOSIT OF MICROORGANISMS FOR THE PURPOSES 0 " PATENT PROCEDURE 136 INTERNATIONAL FORM Diasorm S.R.L. Centre Ricεrche Biomolecolari Via Calataf mi K 1-25122 Brescia RECEIPT IN THE CASE OF AN ORIGINAL DEPOSIT issued pursuant to Rule 7 1 by the INTERNATION AL DEPOSITARY AUTHO IT Y identified at the bottom ot this page I IDENTIFICATION Of THE MICROORGANISM dentification reference given by die DEPOSITOR Accession numbe r given b> the INTERNATIONAL DEPOSITARY AUTHOR!! G3 DSM 13 096 H SCIENTIFIC DESCRIPTION AND/OR PROPOSED TAXONOMIC DESIGNATION The microorganism identified under I above was accompanied by (X ) a scientific description (X ) a proposed taxonomic designation (Mark with a cross where applicable) III RECEIPT AND ACCEPTANCE nil International Depositary Authoritv accepts the microorganism identified under I above, which was received by it on 1 9 9 9 - 10 - 13 (Date of the original deposit)' IV RECEIPT OF REQUEST FOR CONVERSION The microorganism identified under I above was received by this International Depositary Authoritv on (date ot original deposit) and a request to convert the original deposit to a deposit under the Budaoest Treity was received by it on (date of receipt ot request for conversion) V INTERNATIONAL DEPOSITARY AUTHORITY Name DSMZ-DEUTSCHE SAMMLUNG VON Sιgnatur (s) ot person(s) hav u g die power to rep-eient the MIKROORGANISMEN UND ZELLKULTUREN GmbH International Depositarv Authoritv or of authorized olfic al(s) Address Mascherode- Weg l b D-38124 Braunscnweig 1 tstyc ^ Date 199 9 - 10 - 13 1 Where Rule 6 4 (d) applies such date is the date on which the status ot international depositarv audionrv was acquired Form DSMZ-BP/4 (sole page) 0196 BUDAPEST TREATY ON THE INTERN ATONAL -COGNITION OF THE DEPOSIT OF MICROORGANISMS FOR THE PURPOSES OF PATENT PROCEDURE 137 INTERNATIONAL FORM Diasonn S.R.L. Centro Ricerche Biotrolecolari Via " Calataflmi N 1-25122 Brescia RECEIPT IN THE CASE OF AN ORIGiN AL DEPOSIT issued pursuant to Rule 7 I b> the INTERNATION AL DEPOSITARY AUTrORITY identified at the botton ot this page 1 IDENTI F ICATION Or THE MICROORGA NISM Identiticat on reference given bv die DEPOSITOR Accession number given by die INTERNATION AL DEPOSITARY AUTHORITY HI DSM 13097 II SCIENTIFIC DESCRIPTION AND/OR PROPOSED TAXONOMIC DESIGNATION The microorganism identified under I above was accompanied by (X ) a scientific description (X ) a proposed taxonomic designation (Mark with a cross where applicable) III RECEIPT AND ACCEPTANCE riiis International Depositary Authority accepts die microorganism identified under I above which was -eceived bv it on 19 9 9 - 10 - 13 (Date ot die original deposit)' IV RECEIPT OF REQUEST FOR CONVERSION The microorganism identified under I above was received bv this International Depositary Auϋιo r ιtv on (date ot original depos t) and a request to convert the original deposit to a deposit under the Budapest Treatv was received bv it on (date ot receipt ot request for conversion) V INTERN ATIONAL DEPOSITARY AUTHORI fY Name DSMZ-DEUTSCHE SAMMLUNG VON ot oe-son(s) hiving the power to represent d e MIKROORGANISMEN UND ZELLKULTUREN GmbH International Depositary Authoritv or of authorized Ouicia (>) Address Mascheroder Weg lb D-38124 Braunschweig (/ • ^^ Date 1999 - 10 - 13 ' Wlice Rule 6 4 (d) applies, such date is the dale on which the status of international depositarv authoritv was acquired Form DSMZ-BP/4 (sole page) 0196 BUDAPEST TREATY ON THE INTER AT.O L -COGNITION OF THE DEPOSIT OF MICROORGANISMS FOR THE PURPOSES OF PATENT PROCEDURE 138 INTERNATION AL FOR Diasoπn S . R . L . Centro Ricerc e B_iomplecol ri Via Calataf imi N . 1 - 25122 Brescia RECE'PT IN THE CASE OF AN ORIGINAL DEPOSIT issued Dursuant to Rule 7 I by d e INTERN TIONAL DEPOSITARY AUTHORITY identifiej at the bottom ot tins page I IDENTIFICATION OF THE MICROORGANISM identification reference given bv the DEPOSITOR Accession number given oy the INTERN ATION AL DEPOSITARY AUTHORITY H2 DSM 13098 II SCIENTIFIC DESCRIPTION AND/OR PROPOSED TAXONOMIC DESIGNATION The microorganism identified under I above was accompanied by (X ) a scientific description (X ) a proposeα taxonomic designation (Mark with a cross where applicable) III RECEIPT AND ACCEPTANCE This International Depositarv Authority accepts the microorganism identified under I aaove which was received by it on 1 9 9 9 - 10 - 13 (Date of die original deposit)' IV RECEIPT OF REQUEST FOR CONVERSION The microorganism identified under 1 above was received bv this International Depos tarv Authoritv on (date ot original deposit) and a request to convert the original deposit to a deposit under the Budapest Treaty was received b> it on (date of receipt of request tor conversion) V INTERNATIONAL DEPOSITARY AUTHORITY Name DSMZ-DEUTSCHE SAMMLUNG VON Sigπatur-is) f person(s) having die power to represent the MIKROORGANISMEN UND ZELLKULTUREN GmbH lii'ernational Depositary Authority or ot audioπzed orticιal(s) Address Mascheroder Weg lb D-38124 Braunschweig Date 1999 - 10 - 1 ! ' Where Rule 6 4 (d) applies, such date is the djte on which the status of international depositary authority was acquired Form DSMZ-BP/4 (sole page) 0196

Claims: Claims 1. A nucleic acid molecule representing the genome of a virus/viral agent, said nucleic acid molecule having at least one of the following features: (a) it contains at least one ORF which encodes a polypeptide having the amino acid sequence of (aa) SEQ ID NO: 21 , SEQ ID NO: 25, SEQ ID NO: 27, SEQ ID NO: 29, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 80, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 91 , SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 180, SEQ ID NO: 182, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198 or of (ab) SEQ ID NO: 81 , SEQ ID NO: 122, SEQ ID NO: 181 , SEQ ID NO: 188; (b) it comprises the DNA sequence of SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 20, SEQ ID NO: 24, SEQ ID NO: 26, SEQ ID NO: 28, SEQ ID NO: 30, SEQ ID NO: 31 , SEQ ID NO: 34, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51 , SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 94, SEQ ID NO: 95 SEQ ID NO 96, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO 119, SEQ ID NO: 120, SEQ ID NO: 121 , SEQ ID NO: 125, SEQ ID NO 177, SEQ ID NO: 179, SEQ ID NO: 183, SEQ ID NO: 184, SEQ ID NO 185, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 191 , SEQ ID NO 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO 199, SEQ ID NO: 200, SEQ ID NO: 201 or SEQ ID NO: 202; (c) it comprises portions of at least 80 nucleotides, preferably 100 nucleotides, more preferably at least 500 nucleotides and most preferably at least 2000 nucleotides which hybridize (under stringent conditions) to the complementary strand of the nucleic acid molecule of SEQ ID NO: 26, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96 or SEQ ID NO: 125, SEQ ID NO: 186, SEQ ID NO: 191 , SEQ ID NO: 199; (d) it is degenerate with respect to the nucleic acid molecule of (c) but does not hybridize to the complementary strand of the genome of TT virus; (e) it is at least 50%, preferably at least 60% and more preferably at least 70% identical with the nucleic acid molecule of SEQ ID NO: 26, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 125 or SEQ ID NO: 186, SEQ ID NO: 191 , SEQ ID NO: 199, at least 60%, preferably at least 70% and more preferably at least 80% identical with the nucleic acid molecule of SEQ ID NO: 24, SEQ ID NO: 34, SEQ ID NO: 75, SEQ ID NO: 87, SEQ ID NO: 118 or SEQ ID NO: 179, SEQ ID NO: 187, SEQ ID NO: 195, it contains an ORF or a fragment thereof which is at least 50%, preferably at least 60% and more preferably at least 75% identical with the nucleic acid molecule of SEQ ID NO: 28, SEQ ID NO: 39, SEQ ID NO: 89, SEQ ID NO: 184 or SEQ ID NO: 193, which is at least 60%, preferably at least 70% and more preferably at least 75% identical with the nucleic acid molecule of SEQ ID NO: 77, SEQ ID NO: 120, SEQ ID NO: 177 or SEQ ID NO: 201 , which is at least 50%, preferably at least 60% and more preferably at least 75% identical with the nucleic acid molecule of SEQ ID NO: 30, SEQ ID NO: 40, SEQ ID NO: 78, SEQ ID NO: 90, SEQ ID NO: 121 , SEQ ID NO: 185, SEQ ID NO: 194 or SEQ ID NO: 202, which is at least 50%, preferably at least 60% and more preferably at least 75% identical with the nucleic acid molecule of SEQ ID NO: 79 or which is at least 50%, preferably at least 60% and more preferably at least 75% identical with the nucleic acid molecule of SEQ ID NO: 31 , SEQ ID NO: 38, SEQ ID NO: 76, SEQ ID NO: 88, SEQ ID NO: 119, SEQ ID NO: 183, SEQ ID NO: 192 or SEQ ID NO: 200 or it is a nucleic acid molecule comprising a nucleic acid molecule encoding an amino acid sequence which is at least 35%, preferably at least 40%, more preferably at least 50% and most preferably at least 75% identical with SEQ ID NO: 21 , SEQ ID NO: 25 SEQ ID NO: 27, SEQ ID NO: 29, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61 , SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 80, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 91 , SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 180, SEQ ID NO: 182, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 196, SEQ ID NO: 197 or SEQ ID NO: 198 or it is a nucleic acid molecule encoding an amino acid sequence which is at least 40%, preferably at least 50% and most preferably at least 75% identical with SEQ ID NO: 81 , SEQ ID NO: 122, SEQ ID NO: 181 or SEQ ID NO: 188; (f) parts of it can be amplified under suitable conditions by PCR employing as primers oligonucleotides as defined in SEQ ID NO: 41 and SEQ ID NO: 42 and/or as defined in SEQ ID NO: 115 and SEQ ID NO: 71 or as defined in SEQ ID NO: 11 , SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 32, SEQ ID NO: 73, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101 , SEQ ID NO: 102, SEQ ID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128; SEQ ID NO: 129, SEQ ID NO: 130, SEQ ID NO: 131 , SEQ ID NO: 132, SEQ ID NO: 135, SEQ ID NO: 136, SEQ ID NO: 172, SEQ ID NO: 173, SEQ ID NO: 174, SEQ ID NO: 175, SEQ ID NO: 176 or SEQ ID NO: 203, SEQ ID NO: 204 or SEQ ID NO: 205 or the complementary strand of such an oligonucleotide; and (g) it deviates from any of the above molecules by insertion, substitution, deletion, inversion, duplication, recombination, addition or a combination thereof. 2. A nucleic acid molecule encoding a viral (poly)peptide or a fragment thereof, wherein said nucleic acid molecule (a) contains at least one ORF which encodes a polypeptide having the amino acid sequence of SEQ ID NO: 21 , SEQ ID NO: 25, SEQ ID NO: 27, SEQ ID NO: 29, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 80, SEQ ID NO: 81 , SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 91 , SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO. 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 180, SEQ ID NO: 181 , SEQ ID NO: 182, SEQ ID NO: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 196, SEQ ID NO: 197 or SEQ ID NO: 198 or a fragment thereof of at least 6 amino acids; (b) has the sequence identified in SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 20, SEQ ID NO: 26, SEQ ID NO: 28 , SEQ ID NO: 30, SEQ ID NO: 31 , SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51 , SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121 , SEQ ID NO: 125, SEQ ID NO: 177, SEQ ID NO: 179, SEQ ID NO: 183, SEQ ID NO: 184, SEQ ID NO: 185, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 191 , SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201 or SEQ ID NO: 202 or a fragment thereof of at least 12 nucleotides; (c) has the sequence identified in SEQ ID NO: 24, SEQ ID NO: 34, SEQ ID NO: 75, SEQ ID NO: 87, SEQ ID NO: 118, SEQ ID NO: 179, SEQ ID NO: 187 or SEQ ID NO: 195; (d) hybridizes under stringent conditions to the complementary strand of the nucleic acid molecule of SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 20, SEQ ID NO: 28 ,SEQ ID NO: 30, SEQ ID NO: 31 , SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51 , SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121 , SEQ ID NO: 125, SEQ ID NO: 177, SEQ ID NO: 179, SEQ ID NO: 183, SEQ ID NO: 184, SEQ ID NO: 185, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 191 , SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201 or SEQ ID NO: 202; (e) is degenerate with respect to the nucleic acid molecule of (d) but does not hybridize to the complementary strand of the genome of TT virus encoding TTV ORF1 and/or TTV ORF2; (f) encodes a polypeptide which is at least 35%, preferably at least 40%, more preferably at least 50% and most preferably at least 75% identical with SEQ ID NO: 21 , SEQ ID NO: 25, SEQ ID NO: 27, SEQ ID NO: 29, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 80, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 91 , SEQ ID NO: 92, SEQ ID NO 93, SEQ ID NO: 123, SEQ ID NO: 124 or SEQ ID NO: 180, SEQ ID NO 182, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 196, SEQ ID NO 197, SEQ ID NO: 198 or encodes a polypeptide which is at least 40%, preferably at least 50%, more preferably at least 60% and most preferably at least 75% identical with SEQ ID NO: 81 , SEQ ID NO: 122, SEQ ID NO: 181 or SEQ ID NO: 188; (g) is at least 50%, preferably at least 60%, more preferably at least 75% and most preferably at least 90% identical with the sequence specified in (b) or at least 60%, preferably at least 70%, more preferably at least 80% and most preferably at least 90% identical with the sequence specified in (c); or (h) it deviates by any of the above molecules by insertion, substition, deletion, inversion, duplication, recombination, addition or a combination thereof; or (i) parts of it can be amplified under suitable conditions by PCR employing as primers oligonucleotides as defined in SEQ ID NO: 41 and SEQ ID NO: 42 and/or as defined in SEQ ID NO: 115 and SEQ ID NO: 71 or as defined in SEQ ID NO: 11 , SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 32, SEQ ID NO: 73, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101 , SEQ ID NO: 102, SEQ ID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128; SEQ ID NO: 129, SEQ ID NO: 130, SEQ ID NO: 131 , SEQ ID NO: 132, SEQ ID NO: 135, SEQ ID NO: 136, SEQ ID NO: 172, SEQ ID NO: 173, SEQ ID NO: 174, SEQ ID NO: 175, SEQ ID NO: 176 or SEQ ID NO: 203, SEQ ID NO: 204 or SEQ ID NO: 205 or the complementary strand of such an oligonucleotide. 3. A nucleic acid molecule specifically hybridizing to the complementary strand of the nucleic acid molecule having the nucleic acid sequence of SEQ ID NO: 26, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 125, SEQ ID NO: 186, SEQ ID NO: 191 or SEQ ID NO: 199 specified above or to said nucleic acid molecule or being identical to said nucleic acid molecule or to said complementary strand thereof wherein said nucleic acid molecule comprises at least 12 nucleotides. 4. The nucleic acid molecule of claim 3 wherein said fragment comprises at least 18 nucleotides. 5. The nucleic acid molecule of claim 4 wherein said fragment comprises at least 21 nucleotides. 6. The nucleic acid molecule of claim 5 wherein said fragment comprises at least 25 nucleotides. 7. The nucleic acid molecule of any one of claims 3 to 6 wherein said fragment encodes an epitope that reacts with antibodies specific for SEN virus. 8. The nucleic acid molecule of any one of claims 1 to 7 which is a primer or a probe. 9. The nucleic acid molecule of claim 8 wherein said primer or probe has the sequence SEQ ID NO: 1 1 , SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 32, SEQ ID NO: 41 , SEQ ID NO: 42, SEQ ID NO: 71 , SEQ ID NO: 73, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101 , SEQ ID NO: 102, SEQ ID NO: 115, SEQ ID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128; SEQ ID NO: 129, SEQ ID NO: 130, SEQ ID NO: 131 , SEQ ID NO: 132, SEQ ID NO: 135, SEQ ID NO: 136 or SEQ ID NO: 172, SEQ ID NO: 173, SEQ ID NO: 174, SEQ ID NO: 175, SEQ ID NO: 176 or SEQ ID NO: 203, SEQ ID NO: 204 or SEQ ID NO: 205. 10. The nucleic acid molecule of any one of claims 1 to 8 which is DNA or RNA. 11. The nucleic acid molecule of claims 10 which is cDNA. 12. A vector comprising the nucleic acid molecule of any one of claims 1 to 11. 13. A host cell transfected or transformed with the vector of claim 12. 14. A method of producing a (poly)peptide encoded by the nucleic acid molecule of any one of claims 1 to 11 comprising culturing the host cell of claim 13 under suitable conditions and isolating the (poly)peptide produced from the culture. 15. A (poly)peptide encoded by the nucleic acid molecule of any one of claims 1 to 11 or produced by the method of claim 14. 16. A virus or viral agent carrying the genome represented by the nucleic acid molecule of claim 1. 17. A virus or viral agent having a genomic sequence which comprises at least 3 ORFs, wherein parts of said genomic sequence can be amplified under suitable conditions by PCR employing as primers oligonucleotides as defined in SEQ ID NO: 41 and SEQ ID NO: 42, in SEQ ID NO: 115 and SEQ ID NO: 71 , in SEQ ID NO: 126 and SEQ ID NO: 127, in SEQ ID NO: 128 and SEQ ID NO: 71 , in SEQ ID NO: 172 and SEQ ID NO: 171 , in SEQ ID NO: 174 and SEQ ID NO: 175 or as defined in SEQ ID NO: 203 and SEQ ID NO: 204 or as defined in any one of SEQ ID NO: 11 , SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 32, SEQ ID NO: 73, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101 , SEQ ID NO: 102, SEQ ID NO: 129, SEQ ID NO: 130, SEQ ID NO: 131 , SEQ ID NO: 132, SEQ ID NO: 135, SEQ ID NO: 136, SEQ ID NO: 173, SEQ ID NO: 176 or SEQ ID NO: 205, or an oligonucleotide having a complementary sequence. 18. The virus or viral agent of claim 16 or 17 which is a SEN virus. 19. The virus or viral agent of claim 16 or 17 which is an attenuated virus or chimeric virus. 20. A host cell in vitro infected or transfected with the virus of claim 16, 17, 18 or 19. 21. The host cell of claim 20 which is a hepatic cell, a macrophage, a lymphocyte, an epithelial cell or an osteocyte or a cell (line) derived therefrom. 22. A method for producing the virus or viral agent of claim 16, 17, 18 or 19 comprising culturing the host cell of claim 20 under suitable conditions and isolating the virus from the culture. 23. The virus or viral agent of claim 16, 17, 18 or 19 or produced by the method of claim 22 which is transmissible by blood. 24. A (poly)peptide isolated from viral preparations, wherein said viral preparation comprises a virus or viral agent of any one of claims 16, 17, 18, 19 or 23. 25. An antibody or a fragment or derivative thereof or an aptamer or another receptor specifically recognizing an epitope on the (poly)peptide of claim 15 or claim 24 or on the virus or viral agent of any one of claims 16, 17, 18, 19 or 23. 26. The antibody of claim 25 which is a monoclonal antibody. 27. The antibody derivative of claim 25 which is an scFv fragment. 28. A derivative of the (poly)peptide of claim 15 or claim 24 which is specifically recognized by the antibody or fragment or derivative thereof or an aptamer or other receptor of any one of claims 25 to 27. 29. The derivative of claim 28 which is (semi)synthetically, e.g. chemically produced. 30. The derivative of claim 29 which is produced by peptidomimetics. 31. A hybridoma producing the antibody of claim 26. 32. A fusion protein comprising the (poly)peptide of claim 15. 33. A mosaic polypeptide comprising at least two epitopes of the (poly)peptide of claim 15 or the virus or viral agent of any one of claims 16, 17, 18, 19 or 23 wherein said mosaic polypeptide lacks amino acids normally intervening between the epitopes in the native SEN virus genome. 34. The nucleic acid molecule of any one of claims 1 to 11 , the (poly)peptide of claim 15 or 24, the derivative of any one of claims 27 to 29, the virus or viral agent of any one of claims 16, 17, 18, 19 or 23; or the antibody or fragment or derivative thereof or aptamer or other receptor of any one of claims 25 to 27, the fusion protein of claim 32, the mosaic polypeptide of claim 33, or the primer of claim 8 or 9 which is detectably labeled. 35. A solid phase which is attached to (a) the nucleic acid molecule of any one of claims 1 to 11 ; (b) the (poiy)peptide of claim 15 or 24; (c) the derivative of any one of claims 28 to 30; (d) the virus or viral agent of any one of claims 16, 17, 18, 19 or 23; (e) the antibody or fragment or derivative thereof or an aptamer or other receptor of any one of claims 25 to 27; (f) the fusion protein of claim 32; and/or (g) the mosaic polypeptide of claim 33. 36. A diagnostic composition comprising at least one of (a) the solid phase of claim 35; (b) the nucleic acid molecule of any one of claims 1 to 11 ; (c) the (poly)peptide of claim 15 or 24; (d) the derivative of any one of claims 28 to 30; (e) the virus or viral agent of any one of claims 16, 17, 18, 19 or 23; or (f) the antibody or fragment or derivative thereof or an aptamer or other receptor of any one of claims 25 to 27; (g) the fusion protein of claim 32; (h) a primer or a pair of primers of claim 8 or 9; and/or (i) the mosaic polypeptide of claim 33. 37. A kit comprising at least one of (a) the solid phase of claim 35; (b) the nucleic acid molecule of any one of claims 1 to 11 ; (c) the (poly)peptide of claim 15 or 24; (d) the derivative of any one of claims 28 to 30; (e) the virus or viral agent of any one of claims 16, 17, 18, 19 or 23; or (f) the antibody or fragment or derivative thereof or an aptamer or other receptor of any one of claims 25 to 27; (g) the fusion protein of claim 32; (h) a primer or a pair of primers of claim 8 or 9; and/or (i) the mosaic polypeptide of claim 33. 38. A non-pathogenic derivative of the virus or viral agent of any one of claims 16, 17, 18, 19 or 23. 39. A composition comprising (a) the nucleic acid molecule of any one of claims 1 to 11 ; (b) the (poly)peptide of claim 15 or 24; (c) the derivative of any one of claims 28 to 30; (d) the virus of claim 19; (e) the non-pathogenic derivative of claim 38; (f) the antibody or fragment or derivative thereof or an aptamer or other receptor of any one of claims 25 to 27; (g) the fusion protein of claim 32; and/or (h) the mosaic polypeptide of claim 33. 40. The composition of claim 39 which is a pharmaceutical composition optionally further comprising a pharmaceutically acceptable carrier. 41. The pharmaceutical composition of claim 40 which is a vaccine. 42. A method of detecting the presence of the virus or viral agent of any one of claims 16, 17, 18, 19 or 23 in a sample comprising (a) hybridizing DNA from said sample with the nucleic acid molecule of any one of claims 1 to 11 or the vector of claim 12 under stringent conditions; and (b) detecting the formation of a nucleic acid hybrid. 43. A method of detecting the presence of the virus or viral agent of any one of claims 16, 17,18, 19 or 23 in a sample comprising (a) hybridizing DNA from a sample with a pair of primers of claim 8 or 9; (b) carrying out a PCR or another DNA amplification technique; and (c) detecting the formation of a specific PCR or another amplification product. 44. A method of detecting the presence of the virus or viral agent of any one of claims 16, 17, 18, 19 or 23 in a sample comprising (a) incubating said sample with the antibody or fragment or derivative or an aptamer or other receptor of any one of claims 25 to 27; and (b) detecting the formation of a complex between a (poly)peptide or virus present in said sample and said antibody or fragment or derivative thereof or said aptamer or other receptor. 45. A method for detecting the antibody or fragment or derivative thereof or an aptamer or other receptor of any one of claims 25 to 27 in a sample, comprising (a) incubating said sample with the nucleic acid molecule of any one of claims 1 to 11 , the virus of any one of claims 16, 17, 18, 19 or 23 or the (poly)peptide of claim 15 or 24 or fragments thereof or with the derivative of the (poly)peptide of claim 28, and (b) detecting the formation of a complex between said antibody, said fragment or said antibody derivative or said aptamer or other receptor and said nucleic acid molecule, said virus or said (poly)peptide or said fragments or derivatives. 46. The method of any one of claims 42 to 45 wherein said nucleic acid molecule, at least one of said primers or said antibody or fragment or derivative thereof or said aptamer or other receptor is detectably labeled. 47. The method of claim 46, wherein said label is a tag, a fluorescent marker or a radioactive marker. 48. The method of any one of claims 42 to 47 wherein said sample is or is derived from blood, serum, sputum and/or feces or another body fluid. 49. A substantially isolated preparation of polyclonal antibodies specifically immunoreactive with the nucleic acid molecule of any one of claim 1 to 11 , the (poly)peptide of claim 15 or 24 or the virus of any one of claims 16, 17, 18, 19 or 23. 50. A method of producing antibodies to the nucleic acid molecule of any one of claims 1 to 11 , the (poly)peptide of claim 15 or 23, the derivative of any one of claims 25 to 27 or the virus or viral agent of any one of claims 16, 17, 18, 19 or 23 comprising immunizing an experimental animal with said nucleic acid molecule, (poly)peptide, derivative, virus/viral agent or the non-pathogenic derivative of claim 38 and isolating serum or specific antibodies produced. 51. A method of immunizing an individual against the virus or viral agent of any one of claims 16 to 19 comprising administering to said individual at least one dose of the vaccine of claim 41. 52. A method of propagating the virus or viral agent of claim 16, 17, 18, 19 or 23 comprising culturing the host ceil of claim 19 or 20 under conditions suitable to promote the propagation of said virus/viral agent. 53. A method of propagating the virus/viral agent of claim 16, 17, 18, 19 or 23 in an animal, comprising the inoculation of said animal with said virus/viral agent, parts of said virus/viral agent and/or with material infected by said virus/viral agent. 54. Use of an anti-viral agent for the preparation of a pharmaceutical composition for the treatment of a disease which is related to and/or caused by the virus or viral agent of any one of claims 16 to 18 or 23. 55. Use of the antibody or fragment or derivative thereof or an aptamer or other receptor of any one of claims 25 to 27 for the preparation of a pharmaceutical composition for the treatment of a disease which is related to and/or caused by the virus or viral agent of any one of claims 16 to 18 or 23. 56. The use of claim 54 or 55, wherein said disease is selected from the group consisting of hepatopathies, inflammatory diseases and proliferative disorders. 57. The use of claim 56, wherein said hepatopathy is acute or chronic hepatitis of unknown etiology (NANE-hepatitis). 58. The use of claim 56, wherein said inflammatory disease is Crohn's disease or Lupus erythematosus. 59. The use of claim 56, wherein said proliferative disorder is cancer, preferably liver or colon cancer. 60. A method of treating or preventing a disease in a mammal, preferably a human that is afflicted with the virus/viral agent as identified in any of the preceding claims comprising administering to said mammal one or more doses of an antiviral agent, antibody, fragment or derivative thereof, aptamer or other receptor as defined in any one of the preceding claims.

Inventors: BONELLI FABRIZIO, BONELLI MARCO, DAL CORSO ANDREA, FIORDALISI GIANFRANCO, MANTERO GIOVANNI LORENZO, MATTIOLI SONIA, OLIVERO PAOLO, PRIMI DANIELE, SOTTINI ALESSANDRA, VAGLINI LAURA, BONELLI, FABRIZIO, BONELLI, MARCO, DAL CORSO, ANDREA, FIORDALISI, GIANFRANCO, MANTERO, GIOVANNI, LORENZO, MATTIOLI, SONIA, OLIVERO, PAOLO, PRIMI, DANIELE, SOTTINI, ALESSANDRA, VAGLINI, LAURA
Applicants: BONELLI FABRIZIO, BONELLI MARCO, DAL CORSO ANDREA, DIASORIN S R L, FIORDALISI GIANFRANCO, MANTERO GIOVANNI LORENZO, MATTIOLI SONIA, OLIVERO PAOLO, PRIMI DANIELE, SOTTINI ALESSANDRA, VAGLINI LAURA, BONELLI, FABRIZIO, BONELLI, MARCO, DAL CORSO, ANDREA, DIASORIN S.R.L., FIORDALISI, GIANFRANCO, MANTERO, GIOVANNI, LORENZO, MATTIOLI, SONIA, OLIVERO, PAOLO, PRIMI, DANIELE, SOTTINI, ALESSANDRA, VAGLINI, LAURA
Application year: 1999
Main classification: C12N15
IPC codes: A61K35, A61K38, A61K39, A61K48, A61P1, A61P29, A61P31, A61P35, C07K14, C07K16, C07K19, C12N1, C12N5, C12N7, C12N15, C12P21, C12Q1, G01N33