METHODS FOR DETECTION OF KAPOSI'S SARCOMA-ASSOCIATED HERPESVIRUS-LIKE VIRUS

Abstract: The present invention discloses methods for the detection and identification of Kaposi's sarcoma-associated herpesvirus-like Virus (KSHV)-specific nucleic acid sequences or proteins in biological samples derived from patients diagnosed with multiple myeloma (MM) or monoclonal gammopathy of undetermined significance (MGUS). KSHV-specific nucleic acid sequences are detected in these patients by the utilization of polymerase chain reaction (PCR) or reverse transcription polymerase chain reaction (RT-PCR) to amplify viral-specific sequences indigenous to the tissue/cells of theses aforementioned patients. The present invention also discloses several methods for the prophylactic and/or therapeutic treatment of patients with MM or MGUS. Potential treatment modalities disclosed in the present invention include, but are not limited to: (1) the use of inhibitory nucleic acids (INAs), such as "anti-sense" oligonucleotides, to inhibit various viral processes (e.g., DNA replication, mRNA transcription, and/or protein translation); (2) the use of viral-specific polyclonal or monoclonal antibodies, or biologically-active fragments or derivatives thereof, the binding of which may be used to inhibit initial viral infection, replicative/protein synthetic processes, or for the "delivery" of anti-viral agents conjugated to a portion of the immunoglobulin; (3) the utilization of systemic anti-viral chemotherapeutic agents which inhibit viral infection or replicative/protein synthetic processes; and/or (4) the use of a KSHV-specific vaccine to inoculate individuals and elicit a prophylactic or therapeutic immune responses through the utilization of KSHV-specific nucleic acid sequences or recombinant proteins as inoculates to elicit such immune response(s).

Description: DESCRIPTION METHODS FOR DETECΗON OF KAPOSI'S SARCOMA-ASSOCIATED HERPESVIRUS-LIKE VIRUS This application is a continuation-in-part of U.S. Serial No. 08/800,710 filed on February 14, 1997, which is incorporated herein by reference. Field of Invention The present invention relates to a methods for the detection, identification, and therapeutic treatment of various human diseases which share a common etiology. Specifically, these diseases share the two following characteristics: (1) the demonstration of Kaposi's sarcoma-associated herpesvirus-like virus (KSHV) , also classified as human herpesvirus 8 (HHV-8), nucleic acid sequences (DNA and/or mRNA) or virally-encoded proteins within the cells or tissues derived from patient's diagnosed with a member of these related disease and (2) cells derived from patients diagnosed with a member of these related diseases either produce or require Inter- leukin 6 (IL-6) in vivo or in vi tro . Background of Invention I . Classification Of Kaposi's Sarcoma Prior to the establishment of a relationship between Kaposi's sarcoma (KS) , a multifocal vascular tumor, and the human immunodeficiency virus (HIV) -induced acquired immunodeficiency syndrome (AIDS) , KS remained a relatively obscure pathological entity. First described in 1872 by Moritz Kaposi as "idiopathic pigmented sarcoma of the skin," KS was classically noted in older men of Mediterranean, Eastern European, or Jewish ancestry. In these elderly individuals, this classic form of KS is generally rare and indolent. However, several reports in 1981 linking KS with Pneumocystis carinii pneumonia in homosexuals signaled the initial onset of a highly pathologically-aggressive form of KS developing in individuals with AIDS (AIDS-KS) . See e.g., Friedman-Kien, L., et al., Kaposi's sarcoma and Pneumocystis Pneumonia Among Homosexual Men: New York City and California, 30 MMNR 305-8 (1981); Centers for Disease Control, Follow-Up on Kaposi's Sarcoma and Pneumocystis Pneumonia, 30 MMWR 409-10 (1981) . Additionally, this aggressive form of KS has also been demonstrated in individuals with underlying immunosuppression, such as allograft recipients receiving immunosuppressive therapy (see e.g., Beral, V., Epidemiology of Kaposi's sarcoma, 10 Cancer Survey 5-16 (1991)), and in HIV-negative individuals in equatorial Africa (endemic KS; see e.g., Slavin, G. , et al., Kaposi's sarcomain Mainland Tanzania: A Report of 17 Cases, 23 Br . J. Cancer 349-57 (1979)). KS occurs in four distinct subsets. Classic KS, as previously discussed, is a disease affecting older men, aged 50-80 years, of Mediterranean, Eastern European, or Jewish ancestry. Men are affected 8-17 times more frequently than women. The disease is chronic in nature and affects the lower legs, especially the ankles and soles of the feet. Patients with this classic form of KS generally die of unrelated causes, although occasional patients may die from involvement of the gastrointestinal or pulmonary systems. Moreover, patients with classic KS have a 20-fold increased risk of developing a lymphoproliferative disorder compared with the normal population. See e.g., Safai, B., et al., Kaposi's Sarcoma: A Review and Recent Developments, 44 Cancer 419 (1981) . Endemic African KS primarily affects the sub-Saharan, eastern region of the continent, where it accounts for 3- 18% of all neoplastic disease in black patients. See e.g., Davies, J.N.P. & Loethe, F., Kaposi's Sarcoma in African Children: 10 Years of Experience in Johannesburg Hospital (1980-1990), 51 Oncology 63-9 (1994). As in classic KS, endemic African KS has also been found concomitantly with lymphoma, although neither form of KS is clearly associated with overt immunodeficiency. However, an AIDS-associated form of African KS has been described in HIV-positive African patients but its mode of transmission is primarily through heterosexual contact, in contrast to the AIDS-associated KS seen in Europe and the United States. The etiology of iatrogenic immunosuppression-related KS primarily involves the utilization of immunosuppressive medications following allogenic transplantation. KS has been shown to develop in approximately 0.5% of organ transplant recipients, but accounts for 3-6% of all malignancies which develop within this population 10-22 months post-transplantation. See e.g., Farge, D. , Kaposi's sarcomain Organ Transplant Recipients, 2 European J. Med. 339-43 (1993) . For example, renal transplant recipients generally are at the highest risk level, with estimates of 150-200 times more likely than the general population to develop classic KS . Interestingly, the immunosuppressive drug, cyclosporin, appears to be involved with not only a higher incidence, but a more severe form of KS in transplant patients than other commonly-utilized immunosuppressive drugs. The final subset of KS categorization, epidemic AIDS- associated KS is the most common neoplasm of AIDS patients in Europe and the United States. The overall risk of developing KS in AIDS patients has been estimated to be 20,000-times higher in these individuals than the general population. In a recent study it was found that homosexual and bisexual men with AIDS run an approximately 60% risk of developing KS . Moreover, 75% of theses AIDS patients had CD-positive T-cell counts of < 200/mm at the time of initial KS diagnosis. See Orfanos, C.E., et al., Kaposi's Sarcoma: A Reevaluation, 139 Recent Resul ts Cancer Res . 275-96 (1995) . The progression of AIDS- associated KS generally correlates to the clinical severity of the various, concomitant HIV-related illnesses which are experienced by the patient, with aggressive KS being associated with symptomatic HIV infection and lower CD 4 -positive T-cell counts. A. Etiology of Kaposi's Sarcoma The degree of "clustering" of KS in well-defined populations, as well as its relation to immunosuppression initially suggested that an infectious agent may be involved in the pathogenesis of this disease. Several agents were initially investigated as potential etiologic factors, including: cytomegalovirus (CMV) , human papilloma virus (HPV) , hepatitis B virus, Epstein-Barr virus (EBV) , and the bacterium Mycoplasma penetrans . See e.g., Zalla, M.J., Kaposi's sarcoma: An Update, 22 Derma tol . Surg. 274- 87 (1996). In addition, non-biological, non-infectious environmental agents (e.g., amyl nitrate inhalants, nitrous oxide gas) were also examined for a possible etiologic role in KS neoplasia. Unfortunately, however, extensive investigation has yet to provide an etiologic role for these aforementioned agents. In 1994, Chang, et al. utilized representational difference analysis (RDA) to produce "simplified representa-tions" of the genomes of both normal and diseased tissues (e.g., Kaposi's sarcoma), obtained from the same individuals. RDA involves an application of the polymerase chain reaction (PCR) to amplify short-length restriction fragments. These amplified products were then analyzed to determine whether there were any differences in the amplification products of the KS and normal tissues, as well as whether these amplification products exhibited sequence homology to any known infective agents. See Chang, Y., et al., Identifica-tion of Herpesvirus- Like DNA Sequences in AIDS-Associated Kaposi's Sarcoma, 266 Science 1865-9 (1994); PCT Publications WO 96/15779 and WO 96/06159. The high overall degree of homology exhibited by these PCR-amplified genomic sequences was suggestive of their belonging to a novel, previously unidentified member of the gammaherpesvirus subfamily. The new herpesvirus was subsequently referred to as Kaposi's sarcoma-associated herpesvirus-like virus (KSHV) and provisionally designated human herpesvirus-8 (HHV-8). See e.g., Roizman, B., New Viral Footprints in Kaposi's Sarcoma, 332 New Engl . J. Med. 1227-29 (1995). KSHV-specific sequences have now been detected in < 90% of biopsy specimens from HIV-1-associated, classical, endemic African, and immunosuppression- associated, post-trans-plantation Kaposi's sarcoma lesions. See e.g., Schalling, M., et al . , A Role for a New Herpesvirus (KSHV) in Different Forms of Kaposi's Sarcoma, 1 Na t . Med. 705-6 (1995) . A putative role for KSHV in the etiology of KS has been suggested by in vivo immunofluorescence serologic data which has demonstrated that seroconversion to antibodies directed towards KSHV latent nuclear antigens precedes the developement of KS . See Gao, S-J. , et al., Seroconversion to Antibodies Against Kaposi's Sarcoma-Associated Herpesvirus- Associated-Related Latent Nuclear Antigens Before the Development of Kaposi's Sarcoma, 335 New Engl . J. Med. 233-41 (1996) . Most importantly, KSHV-specific sequences have only been shown to be associated with the malignant endothelial and spindle cells in KS lesions, rather than non-neoplastic cells. See Boshoff, C, et al., Kaposi's Sarcoma-Associated Herpesvirus Infects Endothelial and Spindle Cells, 12 Nature Med. 1274-8 (1995) . B. Additional Kshv-Associated Lymphoproliferative Diseases Additionally, two lymphoproliferative disorders related to AIDS (primary effusion lymphoma (PEL) /body cavity-based lymphoma (BCL) and multicentric Castleman's disease (MCD; multicentric angiofollicular hyperplasia) ) have also been associated with KSHV via the detection of KSHV-specific sequences within these tumors. As in Kaposi's sarcoma, the KSHV-specific sequences are associated only with the malignant cells in these lymphoproliferative disorders. See Said, J.W., et al., KSHV in Primary Effusion Lymphoma: Ultrastructural Demonstration of Herpesvirus in Lymphoma cells, 87 Blood 4937-49 (1996); Nador, R.G., et al . , Herpes-Like DNA Sequences in a Body Cavity-Based Lymphoma in an HIV- Negative Patient, 333 New Engl . J. Med. 943-6 (1995); Soulier, J. , et al., Kaposi's Sarcoma-Associated Herpesvirus-Like DNA Sequences in Castleman's Disease, 86 Blood 1276-80 (1995) . Body cavity-based/primary effusion lymphomas are primarily found in the pleural, pericardial, or peritoneal cavities clinically presenting as lymphomatous effusions. They generally exhibit no identifiable tumor mass and have indeterminate immunophenotypes throughout their clinical course. However B-cell genotypes with clonal immunoglobulin rearrangements may be occasionally found. Furthermore, unlike many AIDS-related, non-Hodgkin' s B- cell lymphomas, AIDS-related BCL/PEL almost always contain EBV and KSHV sequences and consistently lack rearrangement of the oncogene c-myc . See e.g., Karcher, D.S. & Alkan, S., Herpes-Like DNA Sequences, AIDS-Related Tumors and Castleman's Disease, 33 New Engl . J. Med. 797-8 (1995). For example, in a recent clinical study, KSHV was detected in 8 AIDS-related body cavity-based lymphomas, but not in any of 34 other AIDS-related lymphomas or 151 non-AIDS- associated lymphoid neoplasms which were investigated. See Cesarman, E., et al., Kaposi's Sarcoma-Associated Herpesvirus-Like DNA Sequences are Present in AIDS-Related Body Cavity-Based Lymphomas, 332 New Engl . J. Med. 1186-8 (1995) . Thus, the strong association of KSHV with various body cavity-based lymphomas, clinically presenting as lymphomatous effusions, in conjunction with their other distinctive clinical, immunophenotypic, and molecular biological characteristics, led to these types of neoplasms being differentiated from other malignant lymphomas occurring in the body cavity. The term primary effusion lymphoma (PEL) to describe these neoplasms is now recommended, and has recently been submitted for inclusion as a new pathological entity in the Revised European- American Lymphoma Classification. See e.g., Nador, R.G., et al., Primary Effusion Lymphoma: A Distinct Clinicopathological Entity Associated with the Kaposi's Sarcoma-Associated Herpes Virus, 88 Blood 645-56 (1996) . Multicentric Castleman's disease (MCD; multicentric angiofollicular hyperplasia) is an atypical lymphopro- liferative disorder defined using various clinical and pathological characteristics. This disease is generally characterized by polyclonal lymphoproliferation with vascular hyperplasia involving multiple lymphoid organs. As with PEL, MCD is associated with KS in over 75% of diagnosed patients with a concomitant finding of KSHV genomic sequences. See e.g., Peterson, B.A., Multicentric Castleman's Disease, 20 Sem . Oncol . 636-48 (1993). A putative role for KSHV in the etiology of MCD has been postulated with the virus acting as a cofactor (perhaps by growth stimulatory cytokines elaborated by KSHV) in a context of immune dysregulation and suppression, especially in HIV-positive patients. See e.g., Soulier, J., et al., Molecular Analysis of Clonality in Castleman's Disease, 86 Blood 1131-6 (1995) . C. Molecular Biology of KSHV Members of the herpesvirus family establish latent infections for the lifetime of the host. Generally, their large genomes (100-250 Kbp) persist extrachromosomally in latently infected cells as covalently-closed circular genomes. However, when the virus is reactivated (i.e., undergoes lytic infection) , it begins to produce linear forms of the genome to facilitate subsequent packaging into virions. Covalently-closed circular genomes of KSHV have been identified in both KS lesions and PEL of HIV- positive and AIDS patients. However, linear forms of the KSHV genome (indicative of viral replication) were not found in the KS tissue but rather in peripheral blood mononuclear cells. Interestingly, the demonstration of replicative, linear forms of KSHV in peripheral blood monocytes was also found to be associated with the subsequent development of KS in these aforementioned patients. See e.g., Decker, L.L., KSHV is Present as an Intact Latent Genome in KS Tissue but Replicates in the Peripheral Blood Monocytes of KS Patients, 184 J. Exp . Med. 283-8 (1996); Whitby, D., et al . , Detection of Kaposi's Sarcoma-Associated Herpesvirus in Peripheral Blood of HIV-Infected Individuals and Progression to Kaposi's Sarcoma, 346 Lancet 799-802 (1995). As previously discussed, Chang, et al., supra , utilized representational difference analysis (RDA) to produce "simplified representations" of the genomes of both normal and diseased tissues (e.g., Kaposi's sarcoma) obtained from the same individual PCR amplification of short-length restriction fragments. See Chang, Y., et al., Identification of Herpesvirus-Like DNA Sequences in AIDS-Associated Kaposi's Sarcoma, 266 Science 1865-9 (1994). The genomic DNA representation from the diseased tissue was then ligated to a specific priming sequence and hybridized to an excess of non-ligated, normal-tissue DNA representation. Hence, with this RDA method, only unique sequences found in diseased tissue possessing priming sequences on both strands will preferentially undergo amplification during subsequent PCR reaction cycles. Moreover, the use of different ligated priming sequences allowed the sample to be enriched for unique DNA sequences found only in the tissue of interest. Following several cycles of amplification- hybridization from KS and excess normal-tissue genomic DNA, four reasonably discrete DNA bands were demonstrated possessing approximate 380, 450, 540, and 680 bp lengths. The four DNA bands were classified as: KS330Bam , KS390Bam , KS480Bam , and KS 631Bam , respectively. These fragments were characterized following the initial removal of the two flanking, 28 bp ligated primer sequences from the original genomic DNA by Bam HI digestion. Of the four original genomic DNA bands, only KS330J3am and KS631Bai7i were selected for additional analysis by cloning and nucleotide sequencing. Subsequent analysis demonstrated that the KS330Bam fragment is comprised of a 330 bp sequence with a 51% G+C content, whereas the KS63lBam fragment consists of a 631 bp sequence with 63% G+C content. Moreover, KS330Bam possess a 51% amino acid homology to a portion of the ORF26 open reading frame encoding the capsid protein VP23 of Herpesvirus saimiri and a 39% amino acid homology to the sequence encoded by the corresponding BDLFl ORF of EBV. The amino acid sequence encoded by KS631Bam possesses homology to the tegument protein (ORF75) of Herpesvirus saimiri and the corresponding tegument protein of EBV (ORF BNRF1, pl40) . However, no other sequence homology to other herpesviruses is found within the KS631Bam fragment. Subsequently, the 5'- and 3 '-flanking regions of the KS330Bam fragment were cloned and sequenced from a genomic DNA library constructed from KS-tissue obtained from a single KS patient. This served to extend the contiguous sequence flanking both sides of KS330Bam to a total of 1853 bp. A contiguous ORF extending from bp 633 to 1550 (which includes the KS330Bai72 sequence) was later found to be homologous to the ORF26 and BDLFl ORFs of Herpesvirus saimiri and EBV, respectively. See e.g., Albretch, J-C, et al., Herpesvirus saimiri ORF26 Displays Sequence Homology with the BDLFl ORF of Epstein-Barr Virus (EBV) , 66 J. Virol . 5047-52 (1992). Additionally, significantly lower homologies have also been shown to exist to the corresponding proteins of the gammaherpesviruses : bovine herpesvirus type 4, human herpesvirus 6 (HHV-6) , human herpesvirus 7 (HHV-7), cytomegalovirus (CMV) , and equine herpesvirus 2. Elucidation of the genomic sequence of KSHV/HHV-8, with the exception of a 3 Kbp region at the right-end of the genome which was not amenable to cloning, has recently been brought to fruition by mapping of contiguous, overlapping viral genomic DNA inserts from a BC-1 genomic library. BC-1 is a PEL in vi tro cell line (i.e., a naturally-infected B cell line derived from an AIDS- related body cavity-based lymphoma) which contains high copy numbers of the KSHV genome and is concomitantly co- infected with EBV. See e.g., Cesarman, E., et al., A Primary Effusion Lymphoma-Derived Cell Line Infected with EBV (BC-1) Contains High Copy Numbers of the Kaposi's Sarcoma-Associated Herpesvirus, 86 Blood 2708-14 (1995) . The BC-1-derived KSHV genome was found to consist of a unique 140.5 Kbp coding region flanked by multiple, G+C- rich 801 bp terminal repeat sequences. Moreover, at least 88 ORFs, including 66 with homology to Herpesvirus saimiri ORFs, and 5 internal repeat regions were found to be present in the unique coding region of the genome. See Russo, J.J., et al., Nucleotide Sequence of the Kaposi's Sarcoma-Associated Herpesvirus (HHV-8), 93 Proc . Na t ' l Acad. Sci . 14862-7 (1996). The total overall length of the genome is thought to be between 165 and 172 Kbp, depending upon the specific method utilized in the determination . From the aforementioned sequencing data, the KSHV/HHV-8 genome has been shown to encode homologs to numerous proteins including: complement-binding protein, 3 cytokines (2 macrophage inflammatory proteins and interleukin-6) , dihydrofolate reductase (DHFR) , jbcl-2, interferon regulatory factors, interleukin-8 receptor, neural cell adhesion molecule, and a D-type cyclin, as well as various other viral structural and metabolic proteins. See Russo, J.J., supra . Interestingly, however, only the cytokine interleukin-6 (IL-6) has thus far been demonstrated to be an exogenous growth factor in all three KSHV-associated diseases — KS, PEL, and MCD. Plasmacytomas have been found to be induced in mice by intraperitoneal injection of paraffin oil or pristane both of which are potent inducers of IL-6 biosynthesis. See Potter, M., et al . , Induction of Plasma Cell Neoplasms in Strain Balb/c Mice with Mineral Oil and Mineral Oil Adjuvants, 193 Na ture 1086-7 (1963) . Additionally, massive plasmacytomas have been generated in transgenic mice carrying the IL-6 genomic gene fused to the immunoglobulin G (IgG) heavy chain enhancer. See Suematsu, S., et al., IgGl Plasmacytosis in Interleukin-6 Transgenic Mice, 86 Proc. Nat 'l Acad. Sci . 7547-54 (1989). Recently, a KSHV-encoded homolog of IL-6 has been characterized which retains full biological activity, as demonstrated by its ability to support the growth of the murine plasmacytoma cell line, B9, which undergoes paracrine-dependent apoptosis (i.e., cellular death) in the absence of IL-6 in vi tro . See Moore, P.S., et al., Molecular Mimicry of Human Cytokine and Cytokine Response Pathway Genes by KSHV, 274 Science 593-5 (1996) . Specifically, Open Reading Frame (ORF) K2 of KSHV has now been shown to encode an IL-6-like homolog (vIL-6) comprised of 204 amino acid residues (23.4 Kdal) . The vIL-6 homolog contains a hydrophobic 19 amino acid residue secretory signaling peptide possessing a 24.8% amino acid identity and 62.2% similarity to the human IL-6 protein (hIL-6) . In addition, vIL-6 contains other conserved sequences (e.g., 4 cysteine residues, a tryptophan-rich IRF-binding region, and a potent N-glycosylation site) indigenous to other IL-6 proteins. See Moore, P.S., et al . , supra . Human interleukin-6 (IL-6) is a cytokine (cellular growth factor) possessing a molecular weight of approximately 26 Kdal. It is believed that the biologically-functional conformation of IL-6 is a homodimer. IL-6 is synthesized by mononuclear phagocytes, vascular endothelial cells, fibroblasts, some types of activated T cells, as well as other types of cells generally in response to interleukin-1 (IL-1) and, to a lesser extent, tumor necrosis factor-α (TNF-α) . See e.g., Arai, K. , et al., Cytokines: Coordinators of Immune Responses, 59 Ann . Rev. Biochem . 783-836 (1991) . IL-6 can be detected in the general circulation following gram- negative bacterial infection or TNF infusion and appears to be expressed in response to IL-1 or TNF themselves, rather than antigenic stimulation by bacterial lipopolysaccharides . IL-6 does not cause vascular thrombosis or other similar tissue injury, as is seen with TNF. The two best-characterized biological actions of IL-6 involve its interactions with hepatocytes and B cells. IL-6 serves as a growth factor for activated B cells late in the sequence of B cell differentiation. IL-6 similarly acts as a growth factor for various types of malignant plasma cells (e.g., plasmacytomas and myelomas). Many plasmacytomas which grow autonomously, actually secrete IL-6 as an autocrine growth factor. Moreover, IL-6 can promote the growth of somatic cell hybrids by fusing normal B cells with cells from plasmacytomas (i.e., the hybridomas which produce monoclonal antibodies) . As previously discussed, transgenic mice which over-express IL-6 frequently develop massive polyclonal proliferation of plasma cells. With respect to its action on hepatocytes, IL-6 stimulates the expression of several plasma proteins (e.g., fibrinogen) which contribute to the acute phase response. II . Multiple Myeloma A. Etiology of Multiple Myeloma Multiple myeloma (MM) is a malignancy of terminally- differentiated B-lymphocytes known as plasma cells, primarily localized within the bone marrow (BM) . See Joshua, D.E., Myeloma: New Aspects of Biology, Prognosis, and Treatment, 28 Pa thology 2-7 (1996) . Due to the fact that these malignant plasma cells produce a homogeneous or monoclonal antibody, MM is thus characterized as a monoclonal gammopathy. MM is the most common of the monoclonal ga mo-pathies, accounting for approximately 1% of all malignancies and the second most common hematological malignancy. There is a male disposition for the disease, with the annual rates per 100,000 being 4.7 and 3.2 for males and females, respectively. There are also clear ethnic variations, with an overall incidence rate of between 1-2 per 100,000 in Asians, 4-5 per 100,000 in Caucasians, and up to 10 per 100,000 in African- Americans. MM is generally a disease of older individuals, with a median age of diagnosis of 62 years of age in the United States, whereas only 2% of cases are diagnosed prior to age 40. See Riedel, D.A. & Pottern, L.M., The Epidemiology of Multiple Myeloma (Abstract), 6 Hema tol . Oncol . 225-47 (1992). Alarmingly, over the past decade, there has been a steady increase in the rates of MM in the United States and numerous other world-wide sites. Moreover, this appears to be a function of a true increase in incidence, rather than as a result of improved detection, yet the reason remains unclear. A number of potential risk factors for MM have been suggested. The most well- established of these is exposure to ionizing radiation, with atomic bomb survivors, nuclear weapons industry workers, and survivors of the Chernobyl nuclear power plant accident in the Soviet Union, all displaying statistically-significant increases in the inci-dence of MM. Other occupational risks such as exposure to organic chemicals, rubber and textile industry, wood and paper pulp, and hair coloring product use are less well established. Other factors which may play a role in MM include: (1) genetic predisposition — as demonstrated by the higher incidence in certain ethnic groups, the increased frequency of the B allele of the poly(ADP- ribose) polymerase pseudo-gene in African-Americans, potential HLA associations, and murine models in which specific stains show markedly increased susceptibility and (2) chronic antigenic stimulation as in rheumatoid arthritis, SLE, and certain bacterial infections. See Moscinski, L.C. & Ballester, O.F., Recent Progress in Multiple Myeloma, 12 Hema tol . Oncol . 111-23 (1994). B. Immunopathology of Multiple Myeloma The hallmark of multiple myeloma is the production and secretion of a homogeneous or monoclonal immunoglobulin (M-component/protein) which is an idiotypic protein specific for each individual patient. This M- component is found in the patient's serum and occasionally in the urine. For example, if only the light chain of the immunoglobulin is secreted, it is typically found in the urine and is categorized as a Bence-Jones protein. In contrast, in Waldenstrom' s macro-globulinaemia the M- component is of the immunoglobulin M (IgM) type. The monoclonal immunoglobulin is comprised of two "heavy" polypeptide immunoglobulin chains of a single class and subclass and two "light" immunoglobulin polypeptide chains of a single type. The different type of monoclonal immunoglobulins are designated by letters which correspond to their specific "heavy" chain class — T (gamma) in IgG; α (alpha) in IgA; μ(mu) in IgM; δ (delta) in IgD; and e(epsilon) in IgE. Similarly, their light chain types are indicated by κ(kappa) and λ(lambda). Recent advances in molecular biology have greatly facilitated the elucidation of the identity of the cell in the B-cell ontology from which multiple myeloma develops. Earlier observations, based upon immunophenotypic assays, suggested that MM was a stem cell disease. Molecular techniques have now shown that the malignant cell has already undergone somatic course of the disease, including its clinical progression. In addition, the immunoglobulin gene mutation and the immunoglobulin gene sequences in myeloma remains stable throughout the sequences in multiple myeloma appear to be characteristic of an antigen-driven process. These observations have led investigators in the field to surmise that the clonogenic cell is a late stage, post-germinal centre B-cell which has "homing" properties to the bone marrow (i.e., a memory B-cell or a primitive plasma cell which is still in cell cycle) . The phenotypically normal equivalent of circulating primitive plasma cells has been demonstrated in peripheral blood. Additionally, using the technique of polymerase chain reaction (PCR) , several investigators have found low levels of idiotypic cytoplasmic DmRNA transcripts in IgG and IgA myeloma, which may be suggestive of the existence a "pre-switched" clonal cell in MM. However, it should be noted that the incidence of these cells is extremely rare and their biological significance remains unclear. See MacLennan, I. CM., In Which Cells does Neoplastic Transformation Occur in Myelomatosis?, 182 Curr. Topics in Microbiol . Immunol . 209-16 (1994) . C. Association of Interleukin-6 With Multiple Myeloma Several pleiotropic cytokines (growth factors) appear to be involved in the proliferation and differentiation of normal B-cells. Following the initial activation of B- cells with interleukin-4 (IL-4) and expansion with interleukin-5 (IL-5), interleukin-6 (IL-6) induces the final maturation and differentiation of the B-cell into a mature, immunoglobulin-secreting plasma cell. IL-6 is a pleiotropic cytokine with broad stimulatory activity in many aspects of hematopoiesis . See Dubois, F.H.M., et al., Cellular Growth Factors (Saunders Scientific Press, 1993) . In addition to its role in B-cell maturation and differentiation, IL-6 has been shown to function as a growth factor for murine plasmacytoma cells, human myeloma cells in vivo, and in vi tro myeloma cell lines. IL-6 has been shown to be produced by activated monocytes, osteoblasts and octeoclasts in bone marrow, T-cells, B- cells, fibroblasts, endothelial cells, as well as normal and myeloma bone marrow stromal cells (BMSCs) and myeloma- derived in vi tro cell lines. See Niesvizky, R. , et al . , Biology and Treatment of Multiple Myeloma, 7 Blood Reviews 24-33 (1993). A prominent feature of MM is bone disease, which is related to enhanced osteoclast-mediated bone resorption, uncoupled with an increased rate of new bone formation. This results in osteopenia, lyric lesions, and compression fractures evident in a majority of MM patients upon clinical presentation. Osteoclast activation can be induced by a number of cytokines including IL-1, monocyte/macrophage-colony stimulating factor (M-CSF) , TNF-α, and especially IL-6. These cytokines have been shown to be produced either by the myeloma cells themselves or by the cells within the bone marrow environment of MM patients (i.e., stromal cells). See Lichtenstein, A., et al., Production of Cytokines by Bone Marrow Cells Obtained from Patients with Multiple Myeloma, 74 Blood 1266-73 (1989) . In murine systems, IL-6 plays a critical role in the development and maintenance of plasma cell neoplasms. In human myeloma, IL-6 most likely play a similarly important, although somewhat less ubiquitous role. However, the administration of anti-IL-6 monoclonal antibodies has been shown to abrogate the proliferation of human plasma cells both in vivo and in vi tro, especially in patients with plasmablastic disease. See Bataille, R., IL-6 is a Major Cell Growth Factor In Vi tro and In Vivo Especially in Patients with Terminal Disease, 166 Curr. Topics Microbiol . Immunol . 23-31 (1991). Moreover, a number of studies utilizing biological function assays have shown that serum levels of IL-6 are correlated with disease severity and may have prognostic implications in patients diagnosed with MM. See Hitzler, J.K., et. al., Role of Interleukin-6 in the Proliferation of Human Multiple Myeloma Cell Lines OCI-My 1 to 7 Established from Patients with Advanced Stage of the Disease, 8 Blood 1996- 2004 (1991) . Additionally, soluble IL-6 receptor levels have been shown to be elevated in patients with MM and act as an agonist for IL-6/IL-6 receptor interactions. High levels of soluble IL-6 receptor are generally considered a poor prognostic feature in MM patients. See Joshua, D.E., et al., Prognostic Factors in Multiple Myeloma: What Do They Tell Us About the Pathophysiology of the Disease?, 15 Leukemia and Lymphoma 375-81 (1994) . Nonetheless, it should be noted that elevated levels of IL-6 per se do not cause multiple myeloma and other transforming events must occur within the cell to elicit neoplasia. The "source" of IL-6 in human multiple myeloma remains controversial. See Klein, B., et al., Cytokine Network in Human Multiple Myeloma, 6 Hematol . Oncol , Clin . North Am . 272-84 (1992) . Generally, however, the bone marrow environment has been shown to be capable of producing markedly higher amounts of IL-6 than that which are produced by purified myeloma cells. Hence, IL-6 production may be part of a broad cytokine network complex in which other mediators (e.g., interleukin-1 (IL-1) , interleukin-11 (IL-11) , and tumor necrosis factor- α(TNF α) ) stimulate IL-6 production by accessory populations. See Carter, A., et al., The Role of Interleukin-1 and Tumor Necrosis Factor- in Human Multiple Myeloma, 74 Br . J. Haema tol . 424-31 (1991). IL-1 is involved in the coordinated production of IL-2, IL-4, and IL-6. Various stromal elements in the bone marrow as well as several plasma cell lines are stimulated by IL-1 to produce IL-6 in a dose-dependent manner. See Yee, C, et al., supra. TNF is believed to also play a significant role in B-cell developement and enhances proliferation of MM cell lines in vi tro . See Carter, A., et al . , supra . Recent studies have demonstrated that multiple myeloma cells derived from fresh bone marrow biopsies frequently produce IL-6 constitutively, express IL-6 receptor, and exhibit enhanced DNA synthesis in response to exogenous administration of IL-6. See Kishimoto, T., et al., Inter-leukin-6 and its Receptor: A Paradigm for Cytokines, 258 Science 593 (1992); Hirano, T., et al . , Interleukin-6 (IL-6) and its Receptor: Their Role in Plasma Cell Neoplasia, 9 Int . J. Cell Cloning 166-72 (1991) . The IL-6 receptor is a heterodimer consisting of a 60 Kdal binding protein and a 130 Kdal signal- transducing subunit. The binding protein con-tains both an immunoglobulin domain and an aromatic amino acid-rich motif characteristic of receptors which interact with cytokines sharing a tertiary conformation consisting of four D-helices. The signal-transducing subunit contains similar domains, however the immunoglobulin domain is not specific for IL-6 and can interact with other polypeptides as well. The "clustering" of the 160 Kdal signal- transducing subunits by interactions with cytokines and specific binding proteins is thought to trigger intercellular and intracellular signaling by the IL-6 receptor. Cytokines which have also been shown to utilize the same transducer include oncostatin-M and interleukin- 11. Although these cytokines are potent growth factors in vi tro, their function in vivo is less well documented. Ill . Monoclonal Gammopathy of Undetermined Significance "Monoclonal gammopathy of undetermined significance" (MGUS) is characterized clinically by the production of a monoclonal immunoglobulin component, wi thout concomitant clinical evidence of multiple myeloma, Waldenstrom' s macroglobulinaemia, primary amyloidosis, or other related lymphoproliferative disorders. See Kyle, R.A., Monoclonal Gammopathy of Undetermined Significance, 8 Blood Reviews 135-41 (1994); Kyle, R.A. , "Benign" Monoclonal Gammopathy - After 20 to 35 Years of Follow-Up, 68 Mayo Clin . Proc . 26-36 (1993); Radi, J. , Benign Monoclonal Gammopathy (BMG) , 132 Cur, Topics Microbiol . Immunol . 221-4 (1986). While MGUS patients lack clinically demonstrable malignant B-cell disease, there are several features which are characteristic of this disorder including the presence of increased numbers of bone marrow B-lymphocytes and plasma cells and the presence of monoclonal immunoglobulins in the serum or urine. Similar to those individuals diagnosed with MM, MGUS patients may also sometimes be deficient in protective, normal immunoglobulins . The incidence of MGUS within the general population is considerable, with estimates ranging from 1-11% in the healthy, adult population. See Kyle, R.A., Monoclonal Gammopathy of Undetermined Significance, 26 Sem . Hematol . 176-200 (1989) . Additionally, there appears to be a correlation with age. Approximately 3% of person older than 70 years of age and 1% of those older than 50 years of age in the United States, Sweden, and France have been diagnosed with apparently "benign" monoclonal gammopathy. See Kyle, R.A. , Classification and Diagnosis of Monoclonal Gammapathies . In: Manual of Clinical and Labora tory Immunology, 3rd edi tion (N.R. Rose & H. Friedman, editors) p. 152-67, American Association of Microbiology, Washington, D.C. (1986) . Little quantitative data exists regarding its etiologic determinants, although there is some evidence which suggests that genetic, environmental, occupational, and/or immunological (i.e., chronic antigen stimulation or T- lymphocyte deficiency) factors may be responsible for subsequent developement of MGUS or related disorders. See Pasquanletti, P., et al . , Risk of Monoclonal Gammopathy of Undetermined Significance: A Case-Referent Study, 52 Am . J. Hematol . 217-20 (1996) . Many clinicians have complained that the term "monoclonal gammopathy of undetermined significance" is misleading, because it is unknown at the time of diagnosis whether the monoclonal gammopathy will remain stable and benign, or subsequently develop into one of the associated malignant lymphoproliferative disorders such as multiple myeloma, Waldenstrom' s macroglobulinaemia, primary amyloidosis, or other related disorders. Several studies have examined the potential progression of MGUS into neoplasia. In one recent study, performed at the Mayo Clinic, 1026 patients with monoclonal plasma cell disorders were examined. Of these individuals, MGUS was shown to be the most common disorder, affecting 56% (578) of the patients. In another study, also performed at the Mayo Clinic, 241 patients diagnosed with MGUS were clinically "followed" for periods ranging from 20 to 35 years. Of these individuals, 19% remained stable, 10% had an increase in their serum concentrations of monoclonal immunoglobulin (M-protein) although they did not require chemotherapeutic intervention, 47% died of unrelated, non-neoplastic causes, and 24.5% (59) of the individuals developed serious disease during the median follow-up period of 22 years — 39 patients developed multiple myeloma, 8 primary a yloidosis, 7 Waldenstrδm' s macroglobulinaemia, and other malignant lymphopro- liferative disorders in 5 individuals. See Kyle, R.A., Monoclonal Gammopathy of Undetermined Significance, 8 Blood Reviews 135-41 (1994) . The actuarial rate of malignant transformation was 17% at 10 years and 33% at 20 years and the median interval from initial diagnosis of MGUS to the diagnosis of serious malignant disease was 8.5 to 10.5 years, depending upon the specific disorder. Similar results have been obtained in other studies: (1) Fine, et al . , found 4 of 20 MGUS patients who were followed for 3-14 years subsequently developed malignant disease; (2) Pasqualetti, et al . , found malignancy developed in 18% of 100 MGUS patients followed for 8-13 years; (3) Giraldo, et al., reported that the actuarial risk of the development of malignant disease in 213 MGUS patients was 4.5% at 5 years, 15% at 10 years, and 26% at 15 years; and (4) Blade, et al., demonstrated the actuarial probability of malignant disease development at 5 and 10 years was 8.5% and 19.2%, respectively. See Fine, J,M., et al., The Evolution of Asymptomatic Monoclonal Gammapathies : A Follow-up of 20 Cases Over Periods of 3-14 Years, 205 Acta Med. Scand. 339-41 (1979); Pasqualetti, R., et al., Development of Malignant Lymphoproliferative Disease in Monoclonal Gammopathy, 81 Med. Lav. 308-19 (1990); Giraldo, M.P., et al., Gammapatias Monoclonales de Significado Indeterminado: Aspectos Clinicos, Biolόgicos y Evolutivos de 231 Casos, 36 Sangre 377-82 (1991); Blade, J. , et al., Malignant Transformation and Life Expectancy in Monoclonal Gammopathy of Undetermined Significance, 81 Br. J. Haema tol . 391-4 (1992). The differentiation of the patient with benign gammopathy which will remain stable from one in whom multiple myeloma or related disorders will eventually develop remains highly problematic. The molecular weight/size of the serum M-protein, hemoglobin value, percentage of bone marrow plasma cells, the concentration of urinary light immunoglobulin chains, and the serum concentrations of non-monoclonal immunoglobulins have not proved to be useful for the quantitative differentiation of those individuals who will remain stable from those in whom a malignancy will subsequently develop. As demonstrated in the aforementioned clinical studies, currently, follow-up must be continued indefinitely in MGUS patients as approximately one-fourth of these individuals will subsequently develop MM, primary amyloidosis, or other related lymphoproliferative disorders. Hence, it remains of paramount clinical importance to develop methods to (1) identify the potential risk of developing frank malignant disease in MGUS patients and (2) to attenuate or entirely prevent subsequent malignant transformation in these individuals. VI . Structure Of Bone Marrow And Its Relationship To Malignant Cells In Mm In vitro, the primary human BM stromal monolayer has been shown to exist as a complex mixture of several different cell types including fibroblasts, endothelial cells, and macrophages. Stromal cells have been also been reported to play a crucial role in the growth of plasma cell tumors. For example, a stromal cell "feeder layer," derived from the initial site of plasmacytomagenesis, has been demonstrated to be required for the in vitro survival and expansion of primary murine plasmacytomas. The resultant plasma cell lines are indistinguishable from the tumor grown in vivo, as assayed by isotype of secreted antibody and rearrangement patterns of immunoglobulin loci. See Degrassi, A., et al . , In Vi tro Culture of Primary Plasmacytomas requires Stromal Cell Feeder Layers, 90 Proc . Na t ' l Acad. Sci . 2060-4 (1993). The early neoplastic cell lines established by this method are dependent upon direct physical contact with the stromal layer which provides two stimuli for the plasma cells — IL-6 and a second unknown entity — which cannot be replaced in culture with exogenous, soluble factors. Similarly, human MM in vi tro cell lines, while generally difficult to initially establish, have been cultured by use of bone marrow stromal cells (BMSCs) . See Jernberg, H., et al., 5 Leukemia 255-65 (1991); Okuno, Y., et al., 54 Interna t ' l J. Hema tol . 41-7 (1991); Caligaris-Cappio, F., et al., 77 Blood 2688-93 (1991). The malignant plasma cells in MM are primarily localized to BM and circulate in the peripheral blood only rarely, except in the late stages of plasma cell leukemia. Therefore, the clinical observation that MM is a disease which is highly localized within the BM microenviroment suggests that BMSCs possess some distinctive characteristic which favors a close spatial relationship in vivo with malignant B-cell clones (i.e., the myeloma cells). The interactions between plasma cells and the BM microenviroment in MM have been examined and the following features have been demonstrated. First, MM plasma cells express a wide range of adhesion structures including: proteoglycan syndecan, a receptor for hyaluronan-mediated motility, CD44, CD56, and (frequently) CD11 and CD18. Interestingly, the KSHV genome has been shown to contain a CD56 (N-C7ΛM) homolog. See Moore, P.S., et al., 274 Science 739-41 (1996) . Second, MM plasma cells also secrete cytokines, including IL-lβ and macrophage colony stimulating factor (M-CSF) , which are able to activate BM stromal cells to produce IL-6. See Nemunaitis, J. , et al., Human Marrow Stromal Cells: Response to Interleukin-6 (IL-6) and Control of IL-6 Expression, 74 Blood 1929-34 (1989) . The adhesion of MM cell lines to BMSCs alone, appears to stimulate the secretion of IL-6 by the BMSCs. See Uchiyama, H., et al., Adhesion of Human Myeloma- Derived Cell Lines to Bone Marrow Stromal cells Stimulates Interleukin-6 Secretion, 82 Blood 3712-8 (1993) . In addition to IL-6, BMSCs have also been shown to actively secrete IL-8, which possesses the ability to upregulate the expression of adhesion molecules. See Detmers, P.A., et al., 171 J. Exp . Med. 1155-63 (1990). Third, a number of cytokines released within the BM microenviroment by plasma cells, activated stromal cells, or by activated T- cells (e.g., IL-lβ, TNFβ, M-CSF, IL-3, and IL-6) behave as an osteoclast activating factor (OAF). See Kodma, H., et al., 173 J. Exp . Med. 1291-7 (1991); Kurihara, N., et al., 144 J. Immunol . 4226-31 (1990). Additionally, it has recently been reported that BMSCs from MM patients have a "looser" extracellular matrix environment and are better equipped with adhesion molecules (e.g., integrins, CD54, and CD56) , as compared with BMSCs from normal patients. See Gregorettti, M.G., et al., Characterization of Bone Marrow Stromal Cells from Multiple Myeloma, 18 Leukemia Res . 675-82 (1994). Nonetheless, little is quantitatively known of the mechanisms by which malignant plasma cells adhere to BMSCs and how these normally sessile cells unexpectedly appear in the peripheral circulation. The examination of several cell lines has now indicated that the control of cell differentiation and gene expression may be mediated through adhesive interactions with the extracellular matrix (see Juliano, R.L. & Haskill, S., Signal Transduction from the extracellular Matrix, 120 J. Cell . Biol . 577-81 (1993)) and there is also a growing body of evidence which suggests that growth factors become functionally active when bound to extracellular components such as proteoglycans and laminin (see Thiery, J.P. & Boyer, B., The Junction Between Cytokines and Cell Adhesion, 4 Curr. Opin . Cell . Biol . 782-9 (1992). Moreover, it has also been shown that there is a strict interplay between cytokines and cell adhesion molecules — cytokines may regulate cell adhesion which, in return, may modify the cellular response to cytokines. See Hynes, R.O., Integrins: Versatility, Modulation, and Signaling in Cell Adhesion, 69 Cell 11-24 (1992). Uchiyama, et al., have reported the human myeloma in vi tro cell lines specifically adhere to fibronectin (FN) and that this binding was mediated by βl integrin very- late antigen-4-dependent (VLA-4) and RGD-peptide-dependent mechanisms. Members of the βl and β2 integrin families of adhesion molecules are known to be involved in signalling processes. See Hynes, R.O., Integrins: A Family of Cell Surface Receptors, 48 Cell 549-56 (1987) . For example, VLA-4 has been demonstrated to be involved in the mobilization of extracellular Ca 2+ and synergizes with CD3 in the induction of T-cell proliferation and tyrosine phosphorylation of cellular proteins in vitro . See Noijima, Y., et al., Ligation of VLA-4 on T-Cells Stimulates Tyrosine Phosphorylation of a 105 kD Protein, 175 J. Exp . Med. 1045-9 (1992) . Hence, it has been postulated that the interaction of the βl integrin VLA-4 with FN, or with BM in long-term culture, may induce terminal, normal B-cell proliferation and immunoglobulin secretion. See Roldan, E., et al., VLA- /Fibronectin Interaction is Required for the Terminal Differentiation of Human Bone Marrow Cells Capable of Spontaneous and High Rate Immunoglobulin Secretion, 175 J. Exp. Med. 1739-43 (1992) . The adherence of myeloma cell lines to BMSCs in vitro was found to be partially blocked with monoclonal antibodies specific for βl and β2 integrin, suggesting that these molecules may play a role in the binding of myeloma cells to BMSCs. See Uchiyama, H., et al . , Characterization of Adhesion Molecules on Human Multiple Myeloma Cell Lines, 80 Blood 2306-13 (1992) . In addition, these researchers found that adherence of myeloma cells to either normal or myeloma BMSCs markedly augmented IL-6 secretion suggesting that the adhesion process may induce IL-6 signal transduction in a manner analogous to the role of adhesion molecules in the induction of growth factors in other systems. See Uchiyama, et al., supra . Therefore, BMSCs provide a microenviroment for normal hematopoiesis and may affect developing hematopoietic cells both via direct cell-to-cell interaction and/or by the release of growth and differentiation factors, and may, as a result, play an important role in the pathogenesis of multiple myeloma. Moreover, these findings have led to speculation of a possible scenario based upon mutual interactions between plasma cells and BMSCs which are kept in close spatial proximity by adhesion molecules and are reciprocally influenced by cytokines. These interactions may not only promote malignant cell growth and osteoclast activation, but also sequester the malignant plasma cells within the BM microenviroment. V. KSHV Association in Other Malignant and Non- Malignant Diseases It should also be noted that, while the primary focus of the data presented herein has related to lymphoproliferative, hematologic malignancies, IL-6- dependence (and hence potential KSHV-involvement) may play a role in various other malignant and non-malignant disorders. For example: (1) Genitourinary (e.g., prostate and kidney), and head/neck cancers have all been shown to be dependent upon IL-6. (2) In Alzheimer's disease IL-6 has been demonstrated in the amyloid plaques characteristic of this disease, whereas "normal" brain tissue does not contain significant levels of IL-6. (3) IL-6 has been demonstrated in brain tissue of multiple sclerosis patients (MS) . (4) In the disease scleroderma, the lack of ability to demonstrate an IL-6-association using monoclonal antibodies may be due to the presence of KSHV-encoded IL-6 (vIL-6) . While vIL-6 possesses a high degree of homology to human IL-6 (hIL-6) , it may have key differences in the antibody binding site, thus preventing the binding of the anti-hIL-6 monoclonal antibody. (5) IL-6 has been shown to play a role in the autoimmune diseases SLE and rheumatoid arthritis. Hence, it is postulated that IL-6-dependence may be associated with concomitant KSHV-infection in many, if not all of these aforementioned disease. If an etiologic role for KSHV is subsequently established, then the use of antiviral chemotherapy, immunologic-based therapies, prophylactic/ therapeutic vaccination, and related therapies may prove to be highly efficacious in the amelioration of many of these KSHV/IL-6-associated diseases . Multiple sclerosis (MS) is generally presumed to be a T-cell-mediated, chronic inflammatory disease of the central nervous system (CNS) causing demyelination. Several recent studies have demonstrated a marked increase in IL-6 mRNA expression in the sera and especially in the cerebral spinal fluid (CSF) of MS patients (see Navikas, V., et al., 64 J. Neuroimmunol . 63-9 (1996), as well as in Guillain-Barre syndrome, myasthenia gravis, and polymyositis (see Shimada, K. , et al., 42 Japan . J. Allergology 934-40 (1993) . Similarly, IL-6 has been postulated to play a role in various neurodegenerative diseases such as Alzheimer's disease. For example, IL-6 has only been shown in the primitive CNS plaques in demented Alzheimer's disease patients, whereas those patients with early-disease-stage, diffuse plaques and no dementia had no demonstrable IL-6 expression. See Hull, M. , et al., 777 Ann . New York Acad. Sci . 205-12 (1996) . Rheumatoid arthritis (RA) is a systemic autoimmune disease manifested by chronic polyarthritis, synovial cell proliferation, hypergammaglobulinemia, and polyclonal B- cell activation. IL-6 expression has been found to be elevated in RA and is thought to play a role in its pathogenesis. See Hirano, T., et al., 18 Eur. J. Immunol . 1797-1809 (1988); Hirano, T., 62 Clin . Immunol . Immunopa thol . S60-74 (1992). In addition, bone marrow stromal cells (BMSCs) from both RA and MM patients was demonstrated to be capable of supporting the pre-B-cell cell line DW34 in vitro, whereas BMSCs from healthy donors failed to support growth. See Kaisho, T., et al., 149 J. Immunol . 4088-95 (1992). IL-6 has also been shown to play a role in various genitourinary carcinomas including renal cell carcinoma (see Miki, S., et al., 250 FEBS Letters 607-10 (1989); Takenawa, J. , et al., 83 J. Na t 'l Cancer Insti t . 1668-72 (1991)) and urinary bladder carcinoma in vitro (see Kawai, K., et al., 54 Cancer Res . 2630-32 (1994); Yamamoto, M. , et al., 52 Cancer Res . 5329-33 (1992)) and in vivo (see Siegall, C.B., et al., 50 Cancer Res . 7786-88 (1990). Furthermore, IL-6 may play a possible role as an autocrine and/or paracrine growth factor in prostatic carcinoma. See Okamoto, M. , et al., 57 Cancer Res . 141-6 (1997). V. Current Methods Utilized in the Diagnosis of MM and MGUS Currently, the diagnosis of MM or MGUS is rather complex, and entails numerous quantitative diagnostic tests. See Vescio, R.A., et al . , Multiple Myeloma and Chronic Lymphocytic Leukemia, 3 Curr. Opin . Hema tol . 288- 96 (1996) . Diagnosis is primarily accomplished by electrophoresis of the serum and urine of the patient. The latter evaluation is especially important, as approximately one-quarter of MM patients will have tumors which secrete only the light chain portion of the immunoglobulin (Ig) molecule. This small Ig fragment is rapidly cleared by the kidney and, therefore, may not be electrophoreti- cally-detectable in the serum. If a monoclonal Ig protein is identified in the serum of urine of the patient, an immunoelectrophoresis is then performed to characterize the immunoglobulin subtype, which will aid in the classi- fication of the disease type associated with the monoclonal immunoglobulin. Once identified, it should be determined whether the Ig is derived from a malignant, monoclonal plasma cell proliferation (e.g., MM) or from a non-malignant condition (e.g., MGUS). This differentiation is based upon the amount of Ig present in the serum and/or urine, bone marrow histology, presence or absence of skeletal disease, hyercalcemia, anemia, or renal dysfunc-tion. A bone marrow aspirate and biopsy is also performed to assess plasma cell morphology and infiltration. Generally, a marrow plasma cell percentage greater than 30% with a concomitant monoclonal Ig abnormality is considered to be sufficient for a neoplastic classification, even in asymptomatic patients. Differentiation of MM from MGUS is generally problematic. Plasma cell labeling index, β 2 -microglobulin levels, the presence of J chains in the malignant plasma cells, elevated levels of plasma cell acid phosphatase, reduced numbers of CD4+ T-cells, increased numbers of monoclonal-idiotype-bearing peripheral blood lymphocytes, and increased numbers of Ig-secreting cells in the peripheral blood are all characteristic of MM, yet they are not reliable for the differentiation of MGUS due to overlap. See Kyle, R.A. & Lust, J.A., Monoclonal Gammopathy of Undetermined Signifi-cance . In: Neoplastic Diseases of the Blood (P.H. Wiernik, editor) 571-94 (1991) . Currently, the most commonly utilized method for the "staging" of MM is that developed by Durie and Salmon which is based upon tumor bulk and renal function. This method is frequently deemed by clinicians to be a highly complex system which classifies MM into Stage I, II, or III based upon the amount of monoclonal proteins, hemoglobin level, number of lytic lesions, and serum calcium levels. See Durie, B.G.M. & Salmon, S.E., Clinical Staging System for Multiple Myeloma, 36 Cancer 842-54 (1975) . In addition, interleukin-6 receptor expression, plasma cell labeling index, β 2 -microglobulin, serum albumin, C-reactive protein, thymidine kinase levels, expression of bcl-2 oncoprotein, and lactate dehydrogenase levels, have been examined a possible prognostic factors for MM patient survival. However, only the plasma cell labeling index and β 2 -microglobulin had independent prognostic significance. Levels of soluble IL-6 receptor were found to be associated with shorter survival and doubles the number of patients identified as "high-risk" when combined with the plasma cell labeling index and β 2 - microglobulin prognostic markers. See Tienhaara, A., et al., Serum Immunoreactive Interleukin-6 and C-Reactive Protein Levels in Patients with Multiple Myeloma at Diagnosis, 86 Br. J. Haema tol . 391-3 (1994). In conclusion, the diagnosis of MM and MGUS, and especially the differentiation of these two hematologic disorders, is currently problematic. The present invention discloses methods for the detection of KSHV in patients diagnosed with MM and MGUS by qualitative or quantitative determination of various KSHV-specific nucleic acids and/or proteins which will aid in the diagnosis of the diseases. In addition, it should be noted that quantitative determination of the level of expression of various KSHV-specific nucleic acids and/or proteins may be potentially utilized: (1) to clinically differentiate MM from MGUS, (2) to predict the probability of the MGUS patient subsequently progressing to malignant disease (i.e., MM), (3) as a prognostic tool for predicting both patient survival and the degree of disease severity, and (4) monitoring treatment response in patients . VI . Current Methods Utilized in the Treatment of MM and MGUS The current clinical modalities utilized in the initial therapeutic treatment of MM consist of the administration of alkylating agents with the possible concomitant admini-stration of glucocorticosteroids. For example, the alkylating agent, melphalan (ALKERAN ® ) , has been shown to produce a response in approximately 25% of MM patients, whereas the adjunctive addition of glucocorticosteroids (e.g., dexamethasone) increased the patient response rate to 40%. In addition, the adjuctive use of pamidronate concomitantly with chemotherapeutic agents has been reported to prevent the subsequent development of skeletal complications and the production of IL-6 by BMSCs in MM patients and thus may potentially improve their overall survival rates. See Berenson, J.R., et al., Efficacy of Pamidronate in Reducing Skeletal Events in Patients with Advanced Multiple Myeloma, 334 New Engl . J. Med. 488-93 (1996) ; Savage, A. D. , et al . , Pamidrona te Reduces IL-6 Production by Bone Marrow Stroma from Mul tiple Myeloma Pa tients , 88 Blood 105a (1996) . Furthermore, the addition of infusional vincristine, doxorubicin, adriamycin, and carmustine have also been utilized alone and in combination with dexamethasone. However, several clinical studies have suggested little impact on the overall patient survival rates (median life expectancy of only 3 years) with the added toxicity of these combination chemotherapy regimens, as well as an increased risks of toxicity and infections due to neutropenia. See Peest, D., et al., A Comparison of Polychemotherapy for Primary Remission Induction, 31 Bur. J. Cancer 141-56 (1995) . With respect to maintenance therapy, conventional chemotherapy, while reducing tumor mass and overall levels of circulating monoclonal immunoglobulins, rarely results in the patient achieving a complete hematological response. Typically, most patients enter a "plateau phase" wherein the amount of monoclonal immunoglobulin remains relatively constant and it is generally believed that the remaining tumor cells within the patient at this time-point are relatively quiescent and are refractory to continued chemotherapy. Conventional chemotherapeutic treatment is generally stopped at this point, as its continuation does not lead to improved survival and merely leads to a permanent reduction in bone marrow reserve and increases the risk of developing a secondary leukemia. Human leukocyte interferon- α (IFN-α) has been utilized as an anti-neoplastic maintenance agent in the treatment of MM. See Mandelli, F. , et al., Maintenance Treatment with Recombinant Interferon-alfa-2b in Patent with Multiple Myeloma, 116 New Engl . J. Med. 1430-4 (1990) . However, several recent follow-up studies have demonstrated no impact on overall patient survival with the use of IFΝ-α during the "plateau phase." See Westin, J. , et al., Interferon-alfa-2b Versus No Maintenance Therapy During the Plateau Phase of Multiple Myeloma: A Randomized Study, 89 Br. J. Haema tol . 561-8 (1995) . Additionally, IFN-α has been reported to have numerous potential side-effects and possesses little biological activity in refractory MM cases, which limits its use in many MM patients. IFN-α is frequently combined with multi-agent chemotherapy or given following an initial response to the patient's conventional chemotherapy. See Brownman, G.P., et al . , Randomized Trial of Interferon Maintenance in Multiple Myeloma, 13 J. Clin . Oncol . 2354- 60 (1995) . High-dose myeloablative chemotherapy followed by bone marrow or stem cell transplantation is rapidly becoming the standard of care in patients with aggressive disease. Both single-time and sequential autologous bone marrow transplantation has been demonstrated to achieve five year survival rates as high as 60%, compared to approximately 12% for those receiving multialkylator therapy. See Attal, M., et al., High-Dose Therapy Followed by Autologous Bone Marrow Transplantation in Multiple Myeloma, 86 (Supp. 1) Blood 124a-9a (1995) ., Stem cell selection has also been shown to be effective in reducing the number of malignant cells in autologous transplantation. For example, selection for stem cells of the CD34 + phenotype resulted in a 2.7 to more than 4.5-log reduction in the overall number of myeloma cells, compared with the non-selected leukapheresis products. See Schiller, G., et al., Transplantation of CD34-Positive Peripheral Blood Progenitor Cells Following High-Dose Chemotherapy for Patients with Multiple Myeloma, 86 Blood 390-7 (1995). Treatment of MGUS typically consists of monitoring the plasma and urinary levels of the monoclonal Ig, renal function, serum calcium levels, bone lesions, and various other associated physiological factors. As the disease is non-malignant in nature, treatment modalities which are employed in the treatment of MM are not utilized. See Pasqualetti, P., Risk of Gammopathy of Undetermined Significance: A Case-Referent Study, 52 Am . J. Hema tol . 217-20 (1995) . Therefore, in conclusion, there are no currently approved prophylactic modalities available for the treatment of MGUS and the chemotherapeutic regimens currently employed in the therapeutic treatment of MM are generally complex, highly toxic, non-specific in the "targeting" of neoplastic cells, and non-curative in nature. Hence, there remains an as yet unfulfilled need for protocols which will allow patients diagnosed with MM to be therapeutically treated, as well as the prophylactic treatment of MGUS patients to prevent these individuals from subsequently developing malignant disease. Summary of the Invention Disclosed herein is the novel finding of KSHV- specific sequences within whole bone marrow tissue aspirates, and specifically associated with non-malignant bone marrow stromal cells (BMSCs) , in patients diagnosed with the hematological malignancies multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) . For example, one embodiment of the present invention discloses methods for the detection of KSHV-specific sequences in patients diagnosed with MM, MGUS, or other KSHV/IL-6-associated disease, by utilizing polymerase chain reaction (PCR) or reverse transcription polymerase chain reaction (RT-PCR) to amplify viral-specific nucleic acid sequences indigenous to the tissue/cells of these aforementioned patients. In a preferred embodiment, the present invention may be utilized, but is not limited to, the detection and characterization of KSHV in the whole bone marrow tissue aspirates and bone marrow stromal cells (BMSCs) , as well as in peripheral blood cells, of MM and MGUS patients. In this method, nucleic acid (DNA/RNA) is isolated from the aforementioned cells or tissue and subjected to PCR or RT-PCR amplification. Detection of the MGUS- or MM-specific KSHV viral sequences is accomplished by separation of the amplified sequences by agarose gel electrophoresis, immobilization of the species via Southern transfer (blotting) , and detection by liquid hybridization using a labeled, viral sequence-specific probe. Alternately, in situ hybridization may be utilized to detect/localize viral-specific sequences directly on or within the bone marrow tissue (i.e., the BMSCs) of the MM and MGUS patients. For example, in one embodiment, the present invention discloses a method for the detection of KSHV-specific sequences within whole bone marrow tissue aspirates and in the isolated bone marrow stromal cells (BMSCs) of patients diagnosed with the neoplastic diseases, multiple myeloma (MM) and monoclonal gammopathy of undertemined significance (MGUS) . In a second embodiment the present invention discloses a method for the detection of KSHV in peripheral blood samples of these patients. In another embodiment, the present invention discloses the method for the diagnosis of MM and MGUS. An additional embodiment of the present invention discloses methods for the prophylactic and/or therapeutic treatment of patients diagnosed with a member of these KSHV- and/or IL-6-associated diseases, such as MM or MGUS. Potential treatment modalities disclosed in the present invention include, but are not limited to: (1) the use of inhibitory nucleic acids (INAs), such as "anti-sense" oligonucleotides, to directly inhibit various viral pro- cesses (e.g., DNA replication, mRNA transcription, and protein translation) or to inhibit viral processes through the conjugation of anti-viral agents to the INA molecule; (2) the use of viral-specific monoclonal antibodies, or fragments thereof which possess the same binding affinity, the binding of which may be used to inhibit initial viral infection, replicative/protein synthetic processes, or for the "delivery" of various anti-viral agents conjugated to the immunoglobulin (e.g., to the F c region); (3) the utilization of systemic anti-viral chemotherapeutic agents which inhibit viral infection or replicative/protein synthetic processes; and/or (4) the use of a KSHV-specific vaccine to inoculate individuals and elicit a prophylactic or therapeutic immune response through the utilization of KSHV-specific nucleic acid sequences or recombinant proteins as inoculates to elicit such immune response (s). While the present invention discloses methods for the detection of KSHV-specific sequences in patients diagnosed with multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) , as well as for the prophylactic and/or therapeutic treatment of these diseases, these aforementioned methods are equally applicable to various other human diseases which share a common motif. Specifically, these diseases share the two following characteristics: (1) the demonstration of Kaposi's sarcoma-associated herpesvirus-like Virus (KSHV) nucleic acid sequences (DNA and/or mRNA) or virally- encoded proteins within the cells or tissues derived from patient's diagnosed with a member of these related diseases and/or (2) cells derived from patients diagnosed with a member of these related diseases require or produce interleukin 6 (IL-6) in vivo and/or in vi tro . Thus, due to these common characteristics, this group of diseases may be classified as KSHV- and/or IL-6-associated diseases. Additionally, it should be noted that the prophylactic and/or therapeutic treatment methods disclosed herein may be equally applicable to various other pathological entities in which KSHV and/or IL-6-expression may play a role. These may include, but are not limited to, multiple sclerosis, Alzheimer's disease, rheumatoid arthritis, systemic lupus erythematosis (SLE) , and scleroderma . Description of the Figures The present invention may be better-understood and its advantages appreciated by those individuals skilled in the relevant art by referring to the accompanying drawings wherein: Figure 1: nucleotide sequences of the various oligonucieotide primers utilized in the PCR or RT-PCR amplification of the KS330 233 or KSHV interleukin-6 (vIL-6) genomic sequences. This figure includes SEQ ID Nos. 1-5. Figure 2: detection of KSHV in multiple myeloma bone marrow stromal cell (MM BMSC) DNA by PCR amplification of KSHV-specific KS330 233 sequence. A KS330 233 -specific primer set [SEQ ID No. 1 and No. 2] was utilized in the PCR amplifi-cation of the MM BMSC DNA. Panel A: illustrates the results of agarose gel electrophoresis of the KS330 233 PCR amplification products of MM BMSC DNA. Panel B: illustrates the Southern blot hybridization of KS330 233 PCR amplification products of MM BMSC DNA with a 32 P-labeled, KSHV-specific 30 nt. oligonucieotide complementary to internal viral genomic sequences [SEQ ID No. 3a] . Figure 3: nucleotide sequence of 233 bp KS330 233 PCR amplifi-cation products derived BMSCs of patients diagnosed with MM [SEQ ID No. 6]. Figure 4: detection of vIL-6 mRNA transcripts in the total cellular RNA isolated from the BMSCs of both MM and "normal" patients via RT-PCR utilizing a vIL-6-specific 24 bp primer set [SEQ ID No. 4 and No. 5]. Figure 5: Panel A: nucleotide sequence of the KSHV IL-6 gene [SEQ ID No. 7] . Panel B: inferred amino acid sequence of KSHV IL-6 [SEQ ID No. 8] . Figure 6: in si tu hybridization (ISH) with a biotinylated, KSHV-specific 30 nt . oligonucieotide probe complementary to internal viral genomic sequences [SEQ ID No. 3b] or CD31 probe. Panel A ISH of PEL cell line. Panel B ISH of HL60 cell line. Panel C ISH of BMSCs from MM patient. Panel D ISH of same MM BMSCs using CD34 probe. Detailed Description of the Invention Disclosed within the present application is the heretofor undiscovered finding of KSHV-specific sequences in whole bone marrow tissue aspirates and specifically within the non-malignant bone marrow stromal cells (BMSCs) of patients diagnosed with multiple myeloma (MM) and the related monoclonal immunopathy, monoclonal gammopathy of undetermined significance (MGUS) . This disclosure makes possible the diagnosis of MM by detecting the presence of KSHV in the appropriate cells, and the prevention and treatment of MM by the prevention and suppression of infection with KSHV. Prior to the applicant's invention, other investi- gators examining KSHV's potential etiologic role in other hematologic diseases reported negative results when both non-enriched bone marrow tissue aspirates and isolated malignant plasma cells from MM patients were screened for the presence of KSHV-specific sequences. For example, results by Borg, et al., demonstrated KSHV-specific sequences in 0 of 11 samples of isolated malignant plasma cells from MM patients using a nested PCR method. See Borg, K.L., et al., Detection of Karposi's Sarcoma- Associated Herpesvirus-Like Virus Using Nested PCR, 9 Mol . Cell . Probes 251-8 (1995). Similarly, Pastore, et al., found KSHV-specific sequences in 0 of 12 samples of bone marrow aspirates from patients previously diagnosed with MM using viral sequence-specific PCR amplification. See Pastore, C, et al., Distribution of Kaposi's Sarcoma Herpesvirus Sequences Among Lymphoid Malignancies in Italy and Spain, 91 Br. J. Haema tol . 918-24 (1995). I . Detection of KSHV-Specific Nucleic Acids and/or Proteins in Mm And Mgus Patients Once the presence and location of KSHV in MM and MGUS patients was discovered by the present inventors, detection of KSHV as a means of diagnosis is now available. Standard methods for detection of viral infection are therefore included within the scope of this invention. The following is a description of a number of such methods. A. Immunologic-Based Diagnosis In the practice of the present invention, KSHV may be demonstrated in patients diagnosed with multiple myeloma (MM) or monoclonal gammopathy of undetermined significance (MGUS) by the quantitative or qualitative detection of viral-specific antigens (e.g. virally-encoded proteins or viral nucleic acids) or viral-specific antibodies produced by immunologic reaction in the KSHV-infected host. These may be detected in biological samples such as bodily fluids, solid tissues, and/or isolated cells of MM or MGUS patients. A description of general immunometric assay techniques may be found in Basic and Clinical Immunology, 1th edi tion (D. Sites & A. Terr, editors) (1992) and U.S. Patent No. 4,376,110 and No. 4,098,876, whose disclosures are incorporated herein by reference. In addition, hemagglutination inhibition (HI) and complement fixation (CF) may also be utilized to detect either KSHV-specific antigens or antibodies directed against the virus in biological samples. The biological sample may be derived from any bodily fluid or solid tissue which would potentially contain a KSHV-specific antibody, antigen, or fragments thereof. Suitable bodily fluids include, but are not limited to, serum, plasma, cerebrospinal fluid, lymphocytes, urine, transudates, or exudates. In addition, the biological sample may be derived from bone marrow biopsy tissue of from in vi tro cell cultures. 1. Detection of KSHV-Specific Antibodies Immunoassay methods designed to measure KSHV-specific antibodies may be either competitive or non-competitive binding assays. In competitive binding assays, the sample analyte competes with the labeled analyte for specific binding sites present on a capture reagent, generally immobilized on a solid surface. Competitive analyte- receptor assays generally involve analyte from the test sample, an analyte-analog which is labeled to facilitate detection, and a rate-limiting concentration of the analyte receptor species. These analyte and analyte-analog moieties are subsequently allowed to compete for the limited number of binding sites provided by the receptor species present in the assay mixture. Preferably, the capture reagent is a recombinant protein encoded by KSHV or a related human herpesvirus. Other sources of human herpesvirus-specific proteins, including isolated or partially purified naturally occurring viral proteins, may also be utilized. Competitive binding assays can be further differentiated as being described as homogeneous or heterogeneous in nature. In homogeneous assays, all of the reactants participating in the competition reaction are mixed together and the concentration of analyte is determined by its effect on the extent of binding between analyte receptor and labeled analyte analog. The signal which is observed is a direct function of this binding and can be related to the overall concentration of analyte present in the test sample. U.S. Pat. No. 3,817,837, which is incorporated herein by reference, discloses such a homogeneous, competitive immuno-metric assay in which the labeled analyte analog is a analyte-enzyme conjugate and the analyte receptor is an antibody capable of binding either the analyte or the analyte analog. In general, homogeneous assay systems require both an external instrumentality to determine the result and the prior calibration of the observed signal by separate tests performed with known concentration of the specific analyte in a process known as standardization. While homogeneous assays have dominated competitive immunometric assay system development, such systems are not capable of providing results for the determination of multiples analytes in a test sample in a single-test format not requiring external instrumentalities. Heterogeneous, competitive analyte-receptor assays require separation of the bound labeled analyte or receptor from the free labeled analyte or receptor and a subsequent measurement of either the concentration of the bound or free fraction. Methods for performing these assays are described in U.S. Pat. Nos. 3,654,090, 4,298,685, and 4,506,009, which are incorporated herein by reference. The quantitative or semi-quantitative measurement of analyte concentration utilizing this method cannot be performed without the use of additional tests to calibrate the assay results. Hence, only the presence or absence of the analyte can be determined without additional instrumentation or tests. Recently, however, methods have been developed for the internal calibration of analyte-receptor assays by providing a device which incorporates reference zones whereby the given response at the reference zone represents the assay response for a specific concentration of the analyte. The response gen- erated by the unknown concentration of analyte in the test sample is then compared with the response at the reference zone to determine the concentration of the analyte in the test sample in a quantitative or quantitative manner. U.S. Pat. No. 4,540,659, which is incorporated herein by reference, describes a system which incorporates several analyte concentration standards which provide the ability to make semi-quantitative determinations of analyte concen-trations in competitive analyte-receptor assays via direct visual examination. Non-competitive binding assays are generally performed as a "sandwich" assay, wherein the sample analyte is bound between two analyte-specific binding reagents. Thus, the analyte is detected via its binding to two distinct receptors - where one receptor may be labeled to facilitate subsequent detection and the other is frequently immobilized to a solid-phase to facilitate separation from unbound reaction components (e.g., unbound labeled first receptor) . One of the binding reagents is used as a capture reagent and generally immobilized onto a solid surface; whereas the second binding reagent is labeled and is used to detect the resultant sample analyte/capture reagent complex by direct visual or instrument-based methods. Non-competitive assays generally utilize the receptor component in a substantial excess over the concentration of the analyte to be determined in the assay. A number of combinations of capture and labeled binding reagents can be used, as well as variety of different immunoassay formats, separation techniques, and labels for the detection of KSHV. 2. Detection Of Kshv-Specific Antigens Polyclonal, monoclonal, or non-naturally occurring/ derivative antibodies (e.g., chimeric antibodies, the F ah , or the F c regions) antibodies may be utilized to quantitatively or qualitatively detect viral-specific antigens (e.g., nucleic acids, protein nucleic acids, or peptide/polypeptides) in biological samples such as bodily fluids, solid tissues, and/or isolated cells of patients either suspected of being infected with KSHV or to confirm diagnosis of a KSHV-associated disease. Polyclonal antibodies may be generated by conjugation of an antigen (e.g., selected nucleic acids, peptides, or polypeptides, or preferably a synthetic, viral-specific peptide initially produced by in vi tro translation in a mammalian cell line) to a carrier protein for use as an immunogen. The immunogen conjugate is then used to immunize an inbred strain of mouse (e.g., balb/c) using a standard adjuvant, such as Freund's adjuvant, and a standard mouse immunization protocol. See Harlow, N.C. & Lane, R., An tibodies : A Labora tory Manual (Cold Spring Harbor Press) (1988) . Alternately, polyclonal antibody-containing immune globulin from individuals who have previously been infected with KSHV, or related herpesviruses, may be obtained using standard techniques. See Harlow & Lane, supra. Briefly, immune globulin preparations may be obtained from individual donors who are screened for antibodies directed against KSHV, and plasmas from high- tittered individuals may be pooled. In addition, plasmas from donors may be pooled and assayed for antibodies directed against KSHV, high-tittered pools are then selected for use in detection methods. Monoclonal antibodies may be obtained by various methods familiar to those skilled in the art. Briefly, spleen cells or other antibody-producing lymphocytes from an animal (e.g., mouse) immunized with the desired antigen are immortalized, generally by PEG-based fusion with a myeloma cell. See Kohler & Millstein, 6 Bur. J. Immunol . 511-9 (1976) . Alternative methods of immortalization include, but are not limited to, transformation with Epstein-Barr virus (EBV), retroviruses, oncogenes (e.g., c-myc, c-abl ) , or other similar methods. The "colonies" arising from single immortalized cell (i.e., hybridoma) are screened for the production of antibodies of the desired specificity and affinity for the antigen. The yield of the monoclonal antibodies produced by the hybridoma may be enhanced by various techniques, including injection into the peritoneal cavity of a vertebrate host. In addition, new techniques using recombinant phage antibody expression systems can also be used to generate monoclonal antibodies. See Marks, J.D., et al., 222 J. Mol . Biol . 581-97 (1991); Hoogenboom, H.R., et al . , 19 Nuc . Acids Res . 4133-42 (1991); McCafferty, J. , et al . , 348 Na ture 552-4 (1990) . It is well-known within the relevant fields that it is only necessary to expose an immunocompetent mammal to an appropriate epitope (s) to elicit an immune response and (ostensibly) effective immunoprotection. Epitopes typically consist of small peptides derived from a larger protein molecule. By use of recombinant DNA methods it is generally routine to alter a native proteins primary structure to create derivative epitopes which are identical to or substantially the same as (i.e., immuno- logically-equivalent to) the naturally-occurring epitope. Such derivatives may include, but are not limited to, peptide fragments, amino acid substitutions, amino acid deletions, and amino acid additions to the amino acid sequences encoding the proteins of KSHV. For example, it is well known that certain amino acid residues can be substituted with amino acids of similar molecular weight and polarity without undue effect upon the biological activity of the protein. As human herpesvirus proteins have considerable tertiary structure, and epitopes are generally conformational, any modification should endeavor to preserve conformation in order to produce a protective immune response. Specific regions of the viral-specific proteins may be selected to generate antibodies. As the amino acid sequence may be inferred from the cDNA sequence, the amino acid sequences may be analyzed to determine whether they produce hydrophilic or hydrophobic regions of the encoded protein. In the case of cell membrane proteins, hydrophobic regions are generally found to be associated with the region of the protein molecule which is embedded in the lipid bilayer of the cell membrane; whereas hydrophilic regions are located on the cell surface, in an aqueous environment. In general, hydrophilic protein regions are more immunogenic than hydrophobic regions. Hence, hydrophilic amino acid sequences may be selected and utilized to generate antibodies specific to the virally-encoded protein. The selected peptides may be generated by use of commercially available synthetic machines, or cDNA, or a fragment thereof, may be cloned and expressed and the resulting polypeptide recovered and used as an immunogen. The polyclonal or monoclonal antibodies directed against KSHV nucleic acids or proteins may be labeled using various methods. The "label" utilized on the antibody may be selected from, but is not limited to, the following categories: chromogens/fluorescers, particulate metals or their derivatives, components of catalyzed reactions, chemilumin-escencent compounds, and radioactive isotopic labels. Chromogens include those compounds which absorb light in a distinctive range such that a specific color may be visibly-observed (i.e., dyes), or emit light when irradiated with electromagnetic radiation of a specific wavelength or wavelength range (i.e., fluorescent compounds) . Illustrative colormetric labels include, but are not limited to, biotin and digoxigenin. Illustrative dye types include, but are not limited to, quinoline, acridine, alizarin, cyanine and anthraquinoid dyes. However, the use of dyes may not provide the requisite degree of sensitivity. Fluorescent compound functional groups include, but are not limited to, porphyrins, 2- aminoaphthalene, p,p' -diaminobenzophenone imines, 1,2- benzophenazin, and quaternary phenanthridine salts. Fluorescent compounds included fluorecein isothio-cyanate (FITC) , rhodamine, phcoerythrin, phycocythrin, phycocyanin, alophycocyanin, and Texas Red. Preferable fluorescent compounds absorb light above 400 nm and emit wavelengths D 10 nm higher than the original excitation wavelength. Fluorescent compounds are sometimes preferred over absorptive dyes because the former compounds can provide for multiplication of a "signal." By irradiating a fluorescer with light of a specific wavelength, one may obtain a plurality of emissions, thus providing multiple measurable events. However, "quenching" by proteins and other molecules present in the reaction mixture sometimes must be considered when these types of fluorescent compounds are utilized. Particulate metal sol-based label are obtained by the direct or indirect coupling of the desired reaction component (e.g., antibody) with particles of an aqueous dispersion of a metal, metal compound, or polymer nuclei coated with a metal or metal compound, having a particle size of at-least 5 nm. The term "coupling" is understood within the relevant art to encompass any type of chemical or physical binding, and includes covalent and hydrogen bonding, polar attraction, absorbtion, and absorption. Metals utilized in this labeling method may include, but are not limited to: gold, platinum, silver, copper, and iron. A metal sol is generally defined as a suspension of metal or metal-derivative particles which, due to their extremely small diameter, remain in a suspension solely due to the effects of Brownian motion. The particulate metal sols to be used as labels may be prepared in a number of ways which are in themselves known. For example, the preparation of a gold sol has been described. See Frens, G., et al . , 241 Na tural Physical Science 20 (1973) . Particulate metal sol-based labels are well-suit for use for the in vi tro qualitative or quantitative determination of immunochemical components such as haptens, antigens, and antibodies in an aqueous test medium. Catalyzed reactions may be either enzyme or non- enzyme catalyzed. Considerations which must be taken into account when using an enzyme catalysis-based label include, but not limited to, enzyme stability, turnover rate, sensitivity of the reaction to environmental factors, the nature of the substrate and products, and the effect of conjugation on the enzyme's catalytic properties. Suitable enzymes include alkaline phos- phatase, β-galactosidase, glucose-6-phosphate dehydro- genase, maleate dehydrogenase, and peroxidase. The methods involved in enzymatic labeling are well known within the relevant art. An alternative labeling source is the use of chemilu- minescent compounds. The chemiluminescent source involves a compound which becomes electronically-excited following a chemical reaction and subsequently may either emit light in the visible range or donate energy to a secondary fluorescent acceptor compound. A number of molecular "families" have been found to be chemiluminescent under a wide variety of conditions. These include, but are not limited to, the 2, 3-dihydro-l, 4-phthaiazinedione family (luminol) , the 2, 4, 5-triphenylimidazole family (lophine) , and the para-dimethylamino oxalate-ester family (luciferase) . Radioisotopic labels are widely utilized in immuno- metric assays. The radiolabel may be selected from, but is not limited to, the following radioactive isotopes: 3 H, 14 C, 32 P, 125 I, 131 I, and 35 S . Methods of labeling substances with radioactive labels are well known within the relevant art. See Maniatis, T., et al., Molecular Cloning: A Labora tory Manual , 2nd edi tion (Cold Spring Harbor Press) (1989) . Once labeled, the viral-specific antibody may be employed to identify and quantify its immunologic counterpart (i.e., antibody or antigenic polypeptide) utilizing various methods. For example, the two principle types of enzyme label-based immunoassays are the enzyme- linked immunosorbent assay (ELISA) and the homogeneous enzyme immunoassay, also known as the enzyme-multiplied immunoassay (EMIT ® , Syva Corporation) . In the ELISA system, detection of the immunogen my be achieved by the use of antibodies coupled to a solid phase. The EMIT ® system is dependent upon the deactivation of the enzyme in the tracer-antibody complex; the activity can thus be measured without the need for a separation step, unlike the ELISA system. Immunoassays utilizing radiolabeled antibodies, known as radioimmunoassays (RIAs) , are well- known in the relevant fields. See Laboratory Techniques in Biochemistry and Molecular Biology, 2nd edi tion (North Holland Pub. Co.) (1984). B. Nucleic Acid-Based Detection KSHV-specific nucleic acid sequences (DNA, RNA, PNA, polynucleotide, oligonucieotide, their analogs) may be quantitatively or qualitatively detected in biological samples such as bodily fluids, solid tissues, and/or isolated cells of patients either suspected of being infected with KSHV or to confirm diagnosis of a KSHV- associated disease by the following method: (1) obtaining a sample of bodily fluid or solid tissue from the subject; (2) contacting the sample with a labeled, KSHV-specific nucleic acid probe under hybridization conditions; and (3) determining the presence of the hybridization between the labeled KSHV-specific probe and nucleic acid sequences indigenous to the biological sample, with hybridization being indicative of the presence of KSHV-specific nucleic acids within the sample. Methods to detect viral-specific DNA sequences include, but are not limited to, Southern blotting, single-stranded conformational polymorphism gel electrophoresis (SSCP) , polymerase chain reaction (PCR) , or other DNA-based technique; or for viral-specific RNA species by Northern blotting, reverse transcription PCR, or other RNA-based technique. In addition, in si tu hybridization may be used with either a DNA- or RNA-based probe to detect KSHV-specific sequences in biological samples . Nucleic acid hybridization is a process whereby a single-stranded nucleic acid species is recognized, under the appropriate conditions, by a second, single-stranded nucleic acid species which possesses a complementary sequence, such that the two single-stranded molecules interact, via hydrogen bonding, to form a double-stranded nucleic acid moiety. Complementarity is defined by the Watson-Crick base-pairing rules whereby Guanine (G) bonds to Cytosine (C) ; Adenine (A) bonds to Thymine (T) in DNA and Uracil (U) in RNA. Moreover, due to the fact that nucleic acid sequences will only anneal to complementary sequences, hybridization is a highly selective method for "selecting" nucleic acid sequences of interest from among the numerous sequences frequently found in biological samples. Some of the various methods which are currently utilized within the relevant scientific fields are reviewed in the following citations: Bagnara, T.H., & Leeson, K. , Nucleic Acid Hybridiza tion , CRC Press, New York, (1991); Maniatis, T., et al . , Molecular Cloning, 2nd ed. , Cold Spring Harbor Laboratory, Cold Spring Harbor, New York pp. 86-104 (1986); Dunn, A.R. & Sambrook, J. , 65 Methods in Enzymology, 468 (1980), whose disclosures are incorporated herein by reference. In order to detect and/or quantitate a specific nucleic acid sequence of interest (a target sequence) , a labeled probe, which possesses sequences which are sufficiently com-plementary to those of the target sequence to allow hybridization, is prepared by conventional means which are well known with the relevant fields. The labeled probe is the allowed to interact with the test sample putatively containing the target nucleic acid sequence under the appropriate conditions (i.e., ionic strength, temperature, nucleic acid concentrations, etc.). The probe then hybri-dizes or anneals to the target sequence if it is present within the test sample. The probe/target sequence hybrids may be separated from the non-hybridized probe by the use of one of numerous available techniques and the amount of hybridized labeled probe may then be measured in a qualitative (e.g., autoradiography) or quantitative (e.g., liquid scintillation counting) manner. The overall sensiti-vity of nucleic acid hybridization assays are limited by various factors including the kinetic rate and overall extent of the hybridization reaction, the specific activity of the labeled probe, the method utilized to separate the non-hybridized from the hybridized probe, and the degree of sensitivity with which the labeled probe can be measured. Under ideal conditions, direct hybridization methods, such as that described above, are capable of detecting approximately lxlO 5 to lxlO 6 target molecules in a given sample. Unfortunately, however, the speed, convenience, and economy with which the nucleic hybridization assay may be performed is often inversely proportional to the overall sensitivity of the assay. In contrast, those assay which possess the aforementioned attributes may lack the degree of sensitivity required for many types of applications. For example, molecular biological researchers may need to detect and/or quantitate a specific genetic sequence which represents only a tiny fraction of the organism's genome or of the total messenger RNA (mRNA) population. Thus, there appears to be a dichotomy between the speed, convenience, and economy with which the nucleic hybridization assay may be performed and the overall degree of sensitivity of the assay. Moreover, as a result of the interactions among the various components and component steps of nucleic acid hybridization assays, there is frequently also an inverse relationship between sensitivity and specificity. Measures which are taken to increase the sensitivity of the assay (e.g., increasing the specific activity of the labeled probe) may potentially result in higher percentages of "false positive" assay results. In addition, therefore, the inverse relationship between sensitivity and specificity has also proved to be problematic in the development of nucleic acid hybridization assays with greater sensitivity. Although nucleic acid hybridization assays provide a highly sensitive means for the detection, identification, and quantification of nucleic acids in samples, many of the methods currently employed require the use of "labels" such as radioactive isotopes, enzyme-based catalysis, fluorescent/chromogenic compounds, chemiluminescent compounds, metal sols, etc. in order to quantitate the results of the hybridization reaction. This label is required due to the fact that although a nucleic acid will only hybridize or anneal to its complementary sequence, the presence of the double-stranded hybrid species is undetectable without the presence of a label. For example, labeling of nucleic acids using the radioactive isotopes 32 P or 35 S (which can be introduced into the DNA molecule in the phosphoribose backbone by both in vivo and in vi tro techniques) is commonly utilized. While radioisotopic labeling provides a high level of sensitivity, they have a variety of inherent problems including a potential danger to the user, relatively short half-lives and therefore a short shelf-life. Moreover, the detection of these aforementioned labels frequently requires advances and expensive instrumentalities, as well as highly skilled technicians to run the assay and interpret the results. Presently, nucleic acid hybridization is detected by various techniques including: the observation of changes in the absorbance of an aqueous hybridization reaction, physically isolating the hybridized nucleic acid species from non-hybridized species by chromatographic techniques or hydroxyapatite and subsequently quantitating the hybridized nucleic acid species by techniques such a liquid scintillation counting, sequestering of the nucleic acid hybrids on a solid matrix such as nitrocellulose, or using techniques which allow the visual detection of the hybridization of a labeled probe such as autoradiography. The following issued patents or patent application publications are illustrative of the types of nucleic acid hybridization assay methods which are currently utilized and their respective disclosures are incorporated herein by reference. European Patent Office (EPO) Application 0,130,523 discloses a method for the detection of nucleic acids by a solid support for nucleic acids and an immobilized nucleic acid probe which is capable of undergoing hybri-dization with complementary nucleic acid sequences. The solid support, to which a Nucleic acid may be bound by irradiation, is described a being comprised of a solid substrate possessing reactive groups, a photochemically-reactive intercalation compound or other ligand capable of binding nucleic acids, and a divalent radical which chemically links the solid substrate and the nucleic acid binding ligand. Specifically, the chemically active, surface hydroxyl groups present on the solid substrate (generally comprised of nitrocellulose) are linked by a bifunctional reagent to an amino-substituted compound, which subsequently is photochemically linked to the nucleic acid. The resulting immobilized amino acid is described within the application as being useful in hybridization assays in which the solid support, with the coupled nucleic acid, is allowed to interact with an unknown sample (potentially containing sequences which are complementary to that of the nucleic acid sequestered on the solid support) and a labeled "detection probe." Subsequent analysis of the solid support for the presence of bound "label" (e.g., radioactivity) is illustra-tive of whether hybridization has, or has not occurred, as well as whether the unknown test sample possesses nucleic acid sequences complementary to that of the nucleic acid bound on the solid support member. EPO Application 0,130,515 discloses a method, utilizing dual nucleic acid hybridization, for the detection of the presence of specific nucleic acid sequence within a test sample. In this method, a test sample, containing unknown nucleic acid sequences, is reacted with two nucleic acid "probes" which possess complementarity to two, non-overlapping regions within the nucleic acid sequence to be detected. One of the probes is labeled and soluble in the reaction mixture, whereas the other probe is unlabeled and bound to a solid support member (e.g., nitrocellulose). The reaction is then incubated for a period of time to allow hybridization to occur. Annealing of both nucleic acid probes to the nucleic acid in the test sample occurs only if the sample contains sequences which possess complementarity to the sequences found in the probes. Separation of the dual hybridization product is accomplished by the separation of the solid support from the reaction mixture and detecting the amount of labeled nucleic acid probe annealed to the nucleic acid bound to the solid support. This method is said to provide a means for determining the presence, in a test sample, of a nucleic acid sequence of interest. PCT Published Application WO84/02721 discloses a method for the detection and quantification of bacteria and viruses containing only ribonucleic acid (RNA) . In this method, the RNA from the test sample organism and a labeled probe (containing nucleic acid sequences which are complementary to the RNA of the sample) are allowed to interact under specific hybridization conditions. The resulting annealing between the nucleic acid species is then measured. The method is described as being useful for solution hybrid-ization or hybridization with an immobilized, labeled nucleic acid probe. PCT Published Application WO87/05334 discloses a method for the detection of nucleic acids by the utilization of detection member which is comprised of a solid support (e.g., latex bead) upon which is bound a nucleic acid(s) possessing a defined sequence(s). Annealing of any complementary nucleic acid sequences contained within the test sample to the detection member results in the agglutination of the latex beads, thus allowing direct visualization of a "positive result." United States Patent 4,486,539 discloses a method and device utilized in the detection and identification of bacterial or viral nucleic acids within a test sample. This is accomplished by a one-step "sandwich hybridization" technique which requires two nucleic acid fragments from the genome of the bacteria or virus to be identified which have no sequences in-common. One of the nucleic acid fragments is unlabeled and bound to a solid support (e.g., a nitrocellulose filter membrane) and the other fragment is labeled and is freely soluble within the reaction mixture. Subsequent interaction between the bacterial/viral nucleic acid to be identified and the nucleic acid sequestered on the solid support results in the annealing of complementary sequences to form a "hybrid" molecule. Concomitant annealing of the second, labeled nucleic acid fragment to the nucleic acid sequences within the test sample results in the labeling of the hybrid molecule sequestered upon the solid support member, thus allowing for detection and quantification. As defined herein, "nucleic acid probes" may be comprised of deoxyribonucleic acid (DNA) , ribonucleic acid (RNA), protein nucleic acid (PNA), or a fragment or derivative thereof. "Hybridization" refers to the binding of a probe molecule to a given target sequence in a manner such that the binding is detectable in a different manner from non-target sequences under the appropriate stringency conditions of hybridization. The stringency conditions are a function of, for example, the size of the probe and target nucleic acid sequences, the overall base composition of the probe and target nucleic acids, the number of mismatches and their relative positions within the nucleic acid sequences, the ionic conditions of the hybridization reaction, and the reaction temperature. For example, high stringency may be attained by overnight hybridization at 68°C in 5X SSC, followed by washing at the same temperature in 0.5X SSC. See Nucleic Acid Hybridiza tion : A Practical Approach . B.D. Hames & S.J. Higgins, editors (IRL Press) (1985); Bovinski, M., et al., 238 Analytical Biochemistry 267-84 (1984). The production of nucleic acid probes is well known to those skilled in the relevant arts. DNA probes may be generated, for example, by the insertion of a specific viral DNA sequence into a suitable vector (e.g., bacterial plasmid or bacteriophage) , followed by transformation in a suitable host cell, replication of the viral DNA within the host cell, and isolation of the recombinant molecule. See Maniatis, et al., supra . Alternately, the DNA probe may be generated enzymatically (e.g., nick translation, primer extension, reverse transcription, or PCR) or by chemical synthesis, including the phophoramidite (see Beaucage & Carruthers, 22 Tetrahedron Letters 1859-62 (1981) or triester (see Matteucci, C, et al., 103 Am . Chem . Soc . 3185-92 (1981) methods. If PCR is utilized in conjunction with nucleic acid hybridization, primers are designed to anneal to a specific sequences within the nucleic acid molecule to be amplified. See PCR Protocols : A Guide to Methods and Applications . M. Innis, et al., editors (Academic Press) (1990) . RNA probes may be generated by the insertion of viral DNA or cDNA sequences downstream of a bacteriophage promoter such as T 3 , T 7 , or SP 6 , generally contained within a bacterial plasmid or bacteriophage, and incubating the linearized hybrid molecule with labeled nucleotides and an appropriate DNA-dependent RNA polymerase (e.g., T 7 RNA polymerase) . Additionally, relatively large amounts of various RNAs may be synthesized by using a recombinant single-stranded RNA molecule which possesses a recognition sequence for the binding of an RNA-directed polymerase, preferably Qβ replicase. See U.S. Patent No. 4,786,600. However, multiple steps are still required to insert the specific sequence into a DNA copy of the variant molecule, clone it into an expression vector, transcribe it into RNA, and then replicate it with Qβ replicase. Labeling of the RNA probe molecules may be accomplished by incorporation of labeled (e.g., radioactive isotope, fluorescent, enzymatic, etc.) ribonucle-otides into the synthesis reaction or, alternately, direct radiolabeling of the 3 ' -terminus of viral RNA may be accomplished using cytidine-3 '- [Bis] -phosphate (pCp) and T 4 RNA ligase. See England, R.E. and Uhlenbeck, O.C., Specific Labeling of 3 '-Termini of RNA with T 4 RNA Ligase. 275 Na ture 560-7 (1978) . In si tu hybridization or, more recently, in si tu PCR or RT-PCR may also be utilized to detect the presence of KSHV-specific sequences in a biological sample. In si tu hybridization is a sensitive method for the localization of specific nucleic acid sequences within cells/tissues which is not dependent upon the expression of antigens or "native verses denatured" nucleic acid conditions. In situ hybridization techniques are well known within the relevant fields. See Methods In Enzymology. S. Berger & A. Kimmel, editors (Academic Press) (1987) . In an in situ hybrid-ization, a sample of solid tissue or cells are fixed to a solid support (e.g., glass microscope slide) and contacted with a hybridization at a moderate temperature so to allow the annealing of a labeled, target sequence-specific probe to the nucleic acid sequences putatively contained within the sample. In si tu PCR methods have recently been developed and are described in Heniford, et al., 21 Nuc . Acids Res . 3159-66 (1993); Neuvo, et al . , 17 Am . J. Surg. Pa thol . 683-90 (1993); Bagasra, et al., 326 New Engl . J. Med. 1385-91 (1992). II . Prophylactic and/or Therapeutic Treatment of Human Patients Diagnosed with Kshv-Associated Disease The present invention discloses various methods for the prophylactic and/or therapeutic treatment of individuals diagnosed with KSHV-associated diseases including, but not limited to, multiple myeloma (MM) or monoclonal gammopathy of undetermined significance (MGUS) . For example, one embodiment of the present invention discloses a method for the treatment of KSHV-associated diseases comprised of administering to the subject having a KSHV-associated disease a pharmaceutically effective amount of an anti-viral agent in a pharmaceutically acceptable carrier, wherein the anti-viral agent is effective in the treatment of the subject with KSHV- associated diseases. A second embodiment of the present invention discloses a method for the treatment of KSHV-associated diseases comprised of the administration to the subject a clinically-effective concentration of an inhibitory nucleic acid sequence (e.g., anti-sense sequence) capable of hybridizing to KSHV-specific sequences under such conditions that the inhibitory nucleic acid molecule selectively enters a KSHV-infected cell of the subject, so as to therapeutically treat the subject. Additionally, an anti-viral agent may be directly conjugated to the KSHV- specific inhibitory nucleic acid molecule, thus providing a mechanism for the delivery of these agents. A third embodiment of the present invention discloses a method of prophylaxis or treatment of KSHV-associated disease by administering to the patient at risk for these diseases, a polyclonal or monoclonal antibody, or fragment thereof possessing identical specificity, in a pharmaceutically acceptable carrier, which selectively binds to the herpesvirus and therapeutically treats the subject. Additionally, an anti-viral agent may be directly conjugated to the KSHV-specific antibody or antibody fragment, thus providing a mechanism for the delivery of these agents. Finally, a fourth embodiment of the present invention discloses a method of prophylaxis or treatment of KSHV- associated diseases by administering to the patient at risk for these diseases, a vaccine (derived either through recombinant means or by heat/chemical attenuation of KSHV or a related herpesvirus) so as to therapeutically treat the subject. It should be noted that the potential efficacy of the various MM therapeutic treatment modalities will be quantitatively determined by a modification of the method initially developed by Vescio, R.A. , et al, Quantitative Comparison of Multiple Myeloma Tumor Contamination in Bone Marrow Harvest and Leukapheresis Autografts, 18 Bone Marrow Transplant . 103-10 (1996) . This procedure is utilized to determine tumor "contamination" in bone marrow (BM) and peripheral blood progenitor cell (PBPC) samples in autologous transplantation in multiple myeloma patients. Tumor contamination in these individuals is quantitatively determined by measurement of immunoglobulin variable region (VDJ) sequences (which are unique and do not vary among tumor clones within the same MM patient) from genomic DNA isolated from BM and PBPC samples. Oligonucieotide primers (complementary to the most "unique" VDJ sequences) are utilized for PCR amplification of these immunoglobulin sequences. The assay is made quantitative, by performing replicative PCR amplifications in which the sample DNA is serially diluted with placental DNA until the appropriately sized PCR amplification product is no longer detectable. By performing a total of five PCR amplifications per serial dilution, Poisson statistics may be utilized to calculate the initial tumor contamination based upon the likelihood that a copy of the VDJ gene will be in a give PCR reaction tube and yield a positive result. See Molesh, D.A. & Hall, J.M., Quantitative Analysis of CD34+ Stem Cells Using RT-PCR on Whole Cells, 3 PCR Meth . Applic . 278-84 (1994). With respect to the methods disclosed herein, a quantitative determination of therapy efficacy may be accomplished by measuring unique, highly conserved KSHV- specific sequences within BMSCs and BMMCs from MM patients, rather than the aforementioned VDJ sequences. Accordingly, the amount of KSHV-specific sequences, as determined by PCR amplification, may be inversely proportional to the overall degree of therapeutic efficacy. A. Anti-Viral Therapeutics With the discovery of KSHV/HHV-8 association with multiple myeloma, MGUS, and other monoclonal lymphoproliferative diseases, effective therapeutic or prophylactic protocols to alleviate or prevent the symptoms of herpesvirus-associated disease may be formulated. Due to the viral nature of these diseases, anti-viral agents such as interferons, nucleoside analogs, ribavirin, amantadine, and pyrophosphate analogs of phosphonoacetic acid (Foscarnet) have application for their treatment. See Gorbach, S.L., et al.. In: Infectious Disease, (Saunders, Philadelphia, PA) Ch. 35, p. 289-312 (1992) . Anti-viral agents described herein include those agents or compositions which interact or bind directly to viral products and interfere with the disease process; and excludes those agents which do not directly impact viral replication or viral titer. For example, anti-viral agents described herein do not include immunoregulatory agents which do not directly affect viral titer or bind to viral products. Hence, anti-viral agents are deemed to be effective if they inactivate the virus or otherwise inhibit its infectivity or replication, as well as the alleviation of the KSHV-associated disease symtomology. The various anti-viral agents which will be useful in the treatment of KSHV-associated diseases may be broadly grouped into classes based upon their presumed modes of biological action. These classes included anti-viral agents which act (1) by inhibition of viral DNA polymerase, (2) by targeting other viral enzymes or proteins, (3) by miscellaneous or incompletely understood mechanisms, or (4) by the binding of inhibitory nucleic acid sequences to viral-specific "target" sequences. These aforementioned anti-viral agents may be utilized in combination (i.e., together or sequentially) to achieve a synergistic or additive biological affect or other therapeutic benefit. However, it should be noted that, although these anti-viral agents may be grouped as a function of their putative modes of biological action, the applicants do not intend to be limited by any particular mechanism of anti-viral action, alone or in combination. Moreover, it will also be understood by those individuals skilled in the relevant fields that an anti-viral agent may act upon more than one target in a virus or virus- infected cell or, alternately, through more than one mechanism. 1. Inhibitors of Viral Dna Polymerase Numerous anti-viral agents currently in clinical use or developement are nucleoside analogs which, ostensibly, act through the inhibition of the viral DNA replication, especially through direct inhibition of the viral DNA polymerase. These nucleoside analogs function as alternative substrates for the viral DNA polymerase or as competitive inhibitors of the DNA polymerase substrates. See Cantor, K. & Schimelmann, G.F., Enzyme Catalysis. In: Biophysical Chemistry (Saunders Press, New York, NY) (1990) . Generally, these agents are preferentially phosphorylated by viral thymidine kinase (TK) , if one is encoded by the virus, and/or have higher affinity for viral DNA polymerase than for the host-cellular DNA polymerases, thus resulting in selective anti-viral activity. Many clinically effective anti-viral agents are modified (i.e., "activated") by the host, host cell, or virally-infected host cell metabolic enzymes. For example, acyclovir requires triphosphorylation to obtain its active form, with the first phophorylation performed by the herpesviral TK enzyme, when present. Other conversions/ modifications which have been reported included the conversion of compound HOE 602 to ganciclovir in a three-step metabolic pathway (see Winkler, T., et al., 14 Antiviral Res . 61-74 (1990)) and the phosphorylation of ganciclovir to its active form by, for example, a CMV nucleotide kinase. Where the nucleoside analog is incorporated into the viral DNA, viral replication or other biological activity may be affected in a number a of ways. For example, the analog may act as a chain-terminator, cause increased lability or susceptibility to breakage of the analog-containing DNA, and/or impair the ability of the analog-containing viral DNA to act as a template for viral transcription or replication. See Balzarini, P., et al., 37 Mol . Pharmacol . 402-7 (1990). It should be noted that the indigenous metabolic capabilities of the specific virus can affect the sensitivity of the virus to anti-viral drug, and is thus an important factor in the choice of the anti-viral drug for therapeutic use. The mechanisms of action of various anti-herpetic agents is discussed in De Clercq, T., 32 Antimicrobial Chemotherapy (Suppl. A) 121-32 (1993), and other references cited supra and infra , all of which are incorporated herein by reference. Moreover, the applicants do not intend to be limited to only those antiviral agents discussed supra and infra , and merely offer these as exemplar agents. Acyclovir and ganciclovir are of interest due to their accepted use in clinical settings. Acyclovir, an acyclic analog of guanine, is initially phosphorylated by the herpesvirus TK and then undergoes further phosphorylation to be incorporated as a chain terminator by the viral DNA polymerase during viral replication. Acyclovir possesses therapeutic activity against a broad range of herpesviruses including: herpes simplex types 1 and 2 (HSV-1 and -2), varicella-zoster (VZV) , cytomegalovirus (CMV) , and Epstein-Barr virus (EBV) . It is utilized to treat the following herpesvirus-associated diseases: herpesvirus encephalitis, CMV retinitis, hairy- cell leukoplakia in AIDS patients, EBV infections, neonatal herpesvirus infections, chronic fatigue syndrome, recurrent herpes zoster infections, and chickenpox in immunocompromised hosts. Exemplary initial intravenous and oral dosages are 250 mg/kg/m 2 body surface area, every 8 hours for 7 days, or maintenance doses of 200-400 mg/kg/m 2 body surface area IV or orally to suppress recurrence. Ganciclovir has been shown to be more effective than acyclovir in the treatment of some herpesvirus infections. See Oren, M. & Soble, R.A. , 14 Clin . Infect . Dis . 741-6 (1991). Exemplary initial intravenous and oral dosages are 5 mg/kg twice per day or 2.5 mg/kg three times per day for 10-14 days. Maintenance doses are 5-6 mg/kg for 5-7 days. The utilization of anti-viral drugs and sequential treatments are useful for the treatment of herpesvirus infections and may also be useful for the treatment of KSHV-associated diseases. For example, Snoeck, et al., demonstrated additive or synergistic effects against cytomegalovirus (CMV) when combining anti-herpesvirus drugs (e.g., combinations of Zidovudine [3 ' -azido-3 ' - deoxythymi-dine, AZT] with HPMPC, ganciclovir, Foscarnet [pyrophosphate analogs of phosphonoacetic acid] , acyclovir, valtnex, or HPMC with other anti-viral agents) . In addition, in the treatment of cytomegalovirus retinitis, induction with ganciclovir followed by maintenance with Foscarnet has been suggested as a method to maximize efficacy while concomitantly minimizing the adverse side effects of either treatment alone. See Snoeck, K.H., 11 Eur. J. Clin . Microbiol . Infect . Dis . 1144-55 (1992) . U.S. Patent No. 5,164,395 (assigned to Blumenkopf) and No. 5,021,437 (assigned to Burroughs Wellcome) disclosed the use of a ribonucleotide reductase inhibitor (an acetylpyridine derivative) for the treatment of herpesvirus infections; including the use of the acetylpyridine derivative in combination with acyclovir. U.S. Patent No. 5,175,165 (assigned to Burroughs Wellcome, Co.), also describes an anti-herpetic composition which contains Acyclovir and, for example, 2- acetylpyridine-5- ( (2-pyridylamino) thiocarbonyl) - thiocarbono-hydrazone. Similarly, U.S. Patent No. 5,137,724 (assigned to Stichting Rega, VZW) discloses combinations of thymidylate synthease (TS) and thymidine kinase (TK) inhibitors used as an anti-herpetic agent. A synergistic inhibitory affect on EBV replication using certain ratios of combinations of HPMPC and AZT has also been reported. See Lin, F., et al., 35 Antimicrob. Agents Chemother. 2440-3 (1991). In addition, U.S. Patent No. 5,137,724 describes the utilization of TS inhibitors (e.g., 5-fluoro-uracil and 5-fluoro-2 ' -deoxyuridine) in combination with compounds having viral TK inhibiting activity. See Balzarini, P., et al., 37 Mol . Pharmacol . 402-7 (1990). Additionally, the nucleoside analog BVaraU has been shown to be a potent inhibitor of HSV-1 and -2, EBV, and VZV and possesses greater anti-viral activity than acyclovir in animal models of herpesvirus-induced encephalitis. Cladribine (2-chlorodeoxyadenisine) is a nucleoside analog which demonstrates highly specific anti- lymphocytic activity and thus acts as an immunosuppressive agent. HPMA ( (S) -1- ( [3-hydroxy-2- phosphorylmethoxyl]propyl) adenine) has been shown to be more active than either acyclovir and ganciclovir in the chemotherapy and prophylaxis of various HSV-1 and -2, HSV(TK-), VZV, and CMV infections in animal models and is frequently utilized in advanced cases of herpesvirus- induced disease. See De Clercq, supra . FIAC (fluoroidoarbinosyl cytosine) and its related fluroethyl (FEAU) and iodo (FIAU) also possess potent anti-herpetic activity. Several agents which directly inhibit the viral DNA polymerase without initial processing (i.e., phosphorylation) by the viral thymidine kinase have been shown to possess anti-herpetic activity. These agents include: Foscarnet sodium (trisodium phosphonoformate) , an inorganic pyro-phosphate analog which act by competitively blocking the pyrophosphate binding site of the viral DNA polymerase, Foscavir, and phosphonoacetic acid (PAA) . Foscarnet is generally utilized more frequently due to its decreased toxicity in comparison to PAA and Foscavir. 2. Inhibition of Viral Proteins Other Than DNA Polymerase While anti-viral agents which selectively inhibit viral DNA polymerase are effective in treating herpesvirus infection, viral replication requires not only the replication of viral nucleic acids but the coordinated translation of proteins and other essential molecules. In accord, the present invention contemplates the treatment of KSHV-associated diseases by the utilization of agents which inhibit the viral infective process by selectively targeting viral proteins (other than DNA polymerase) . These agents will function by inhibiting the synthesis or activity of the target viral protein or, alternately, cause the degradation of the target viral proteins following their synthesis. For example, agents which inhibit the synthesis of capsid proteins (e.g., serine protease) , or inhibit an enzyme which is involved in nucleoside synthesis (e.g., dihydrofolate reductase, DHFR) will be useful. Examples of these agents include, but are not limited to: Parazofurin - inhibits OMP decarboxylase; cyclopete- nylcytosine - inhibits CTP synthease; 1- [2- (hydroxymethyl) cycloalkylmethyl] -5-substituted uracils and guanines - inhibits thymidine kinase (TK) ; and carboxyl-containing N- alkyldipeptides - inhibits IMP dehydrogenase and ribonuclease reductase. 3. Miscellaneous Mechanisms of Viral Inhibition Interferon has been shown to inhibit the replication of herpesviruses. See Oren & Soble, supra . However, its use is somewhat limited due to its inherent toxicity. Several new derivative of interferon have been recently described which retain the anti-viral properties but mitigate the toxic side-effects of interferon in its native form. Herpesvirus "activating" compounds (e.g., estrogen, phorbal esters, forskolin, and β-adrenergic blocking agents) to induce the reactiva-tion of the latent herpesvirus may also be useful in treating KSHV-associated diseases. Studies have shown that controlled reactivation over a short time period or reactivation in combination with the simultaneous or sequential administra-tion of an anti-viral agent potentially mitigates the adverse affects of certain herpesvirus infections. See PCT Applica-tion No. WO 93/04683. Poly (I) -Poly (Ci2 U) or Ampligen, is an approved antiviral drug manufactured by HEM Pharmaceuticals, Inc. The preferred route of administration is intravenous injection, with exemplar dosages of 100 to 600 mg/m 2 two to three times per week. Dosages of at least 200 mg/m 2 per week have been demonstrated to be most effective in the treatment of herpesvirus infection. Kutapressin, manufactured by Schwartz Parma, Inc., is a proprietary anti-viral compound derived from the liver. The recommended dosage is 200 to 250 mg/m 2 daily in an average adult weighing 150 pounds. Several other compounds have been shown to possess anti-viral properties, these compounds include, but are not limited to: compounds A.79296 and A.73209 (Abbott); compound 882C87 (Burroughs Wellcome) ; and mappicine ketone (SmithKline Beecham) . See 55 The Pink Sheet 20-9 (May 17, 1993) . 4. Inhibitory Nucleic Acid Sequences The present invention discloses a method for the therapeutic treatment of human subjects, diagnosed with KSHV-associated diseases (e.g., multiple myeloma (MM) or monoclonal gammopathy of undetermined significance (MGUS) ) , comprised of the in vivo administration of sufficient concentrations of inhibitory nucleic acids (INAs) so to have an affect on the infective, replicative, or protein synthetic activity of KSHV. The utilization of INAs to inhibit viral replication is known within the relevant fields. For example, the INA ISIS 2922 (ISIS Pharmaceuticals, Inc.) has been shown to possess an inhibitory affect on the in vivo and in vitro replication of the gammaherpesvirus cytomegalovirus (CMV) . See Richmond, F.K., 14 Biotechnology News 5-6 (1996). INAs may be introduced into the cell through various techniques, which will be discussed in a subsequent section, and are typically single-stranded species which, through the process of Watson-Crick hydrogen bonding, bind to complementary, target nucleic acid sequences, thus forming a DNA/DNA, RNA/DNA, or RNA/RNA duplex or triplex molecule. INAs are typically referred to as "anti-sense" oligonucleo-tides, as they often possess complementarity to the coding or sense strand of the sequence (i.e., gene) of interest. However, the term "inhibitory nucleic acid" or "INA, " as used herein, refers to both sense and anti- sense nucleic acids, as recent methods have been described which utilize sense oligonucleotides. INAs are frequently utilized both in vivo and in vitro to inhibit various biological functions of a specific target nucleic acid species. Inhibition of the target nucleic acid species may occur, for example, by such processes as: inhibition of DNA replication, inhibition of DNA transcrip-tion, alteration/inhibition of post-transcriptional process-ing of mRNA (e.g., poly (A) addition) , inhibition of mRNA translation, or by alteration of various cellular "house-keeping" mechanisms (e.g., RNA degradation). See e.g., Helene, C. & Toulme, J., Inhibition of Cellular Processes by the Use of Anti- Sense Oligonucleotides: A Review, 1049 Biochim . Biophys . Acta 99-125 (1990) , whose disclosure is incorporated herein by reference. Hence, the utilization of INAs may encompass numerous approaches to altering and/or inhibiting the replication or expression of KSHV/HHV-8 in the BMMMs or BMSCs of patients diagnosed with MM or MGUS. Generally, INA therapeutic approaches may be differen-tiated into those which target genomic DNA sequences, those which target RNA sequences (including pre-mRNA and mature mRNA) , those which target proteins (sense strand approaches), and those which facilitate the cleavage or chemical modification of target nucleic acid species. Approaches which target genomic DNA sequences can be further dif-ferentiated into several sub- categories. First, INAs can be designed to bind to the major helical groove of "native" duplex DNA, thus forming a triplex helical species. Additionally, INAs may be designed to bind to regions of single-stranded DNA resulting from "melting" of the native, double-stranded DNA during replication or transcription. Perhaps the most-common utilization of INAs is their use in binding to target RNA species, such as mRNA precursors (pre-mRNA) or mature mRNA molecules. For example, INAs may be used to inhibit the maturation of pre-mRNAs or, alternately, they may be designed so as to interfere with mRNA, splicing, processing, or translation. By targeting mRNA, INAs may be utilized to interfere or block the translation of the protein encoded by the specific mRNA species. Moreover, this method may be used to selectively suppress certain cellular functions by inhibiting the translation of the mRNA encoding a critical cellular protein. Recent studies have shown that inhibition of translation by the use of INAs involves several different mechanisms of action within the cell to affect protein biosynthesis. For example, INAs have been used to inhibit the in vi tro expression of the c-myc gene product in the human promyelocytic leukemia cell line HL60, which overexpresses the c-myc proto-oncogene . See Wickstrom, E.L., et al., Overexpression of c-myc in the Human Promyelocytic Leukemia Cell Line HL60, 85 Proc . Na t ' l Acad. Sci . 1028-32 (1988). INAs may be utilized to target the "sense" or protein-coding strand of either a specific genomic DNA sequence or an mRNA species to compete with or "trap" the enzyme or binding protein involved in the translation of the given mRNA. See Helene & Toulme, supra . INAs may also be used to induce cleavage or chemical modification/inactivation of the target genomic DNA or mRNA species. Chemical inactivation may be achieved by the induction of cross-links between the INA and the target nucleic acid within the cell. Other types of chemical modifications of target nucleic acids may be induced by the use of appropriately derivatized INAs. Cleavage, and hence inactivation, of the target nucleic acid may be obtained by the conjugation of a chemical or enzymatic substituant to the INA which can be subsequently activated to induce cleavage (either chemical or enzymatic) of the target nucleic acid species. Alternately, cleavage may be facilitated by the utilization of ribozymes or catalytic RNA moieties. In this method, the INA species would be comprised of either a naturally- occurring RNA (ribozymes) or a synthetic nucleic acid species with indigenous catalytic activity. INAs may be developed which inhibit, for example, the genomic DNA sequences and/or the mRNAs which encode either IL-6 or the IL-6 receptor. BMSCs in MM patients have been reported to express IL-6 receptors and secrete IL-6, hence these molecules may be potentially efficacious targets for INA- based anti-viral therapies. While INAs have the potential to be highly effica- cious in the treatment of viral infection in vivo, they nonetheless possess certain inherent problems. Major difficulties associated with the utilization of INAs include nuclease susceptibility, the delivery of the nucleic acid to the target cell in vivo, and the subse- quent "uptake" (i.e., internalization) of the INA by that given cell. Several methods now exist to facilitate such delivery including: (1) conjugation of INA to a moiety which possesses the ability to bind to a specific receptor on the surface of the target cell, thus facilitating internalization of the conjugate; (2) retroviral vectors; (3) cationic lipids; (4) liposomes; and (5) modification or derivitization of the constituent nucleic acids of the INA (i.e., phosphorothioates and methylphosphorothioates) . Natural phosphodiesters (PDs) are not resistant to nuclease hydrolysis, thus high concentrations of oligonucleotides are necessary to achieve an inhibitory effect. See Stein, CA. & Cohen, J.S., Oligonucleotides Inhibitors of Gene Expression: A Review, 48 Cancer Rev. 2659-74 (1989) . To overcome nuclease hydrolysis, modified PD analogs such as phosphorothioates (PTs) and methyl- phosphonates (MPs) have been developed. See Miller, P..S., et al., Biochemical and Biological Effects of Nonionic Nucleic Acid Methyl-phosphonates and Phosphorothioates, 20 Biochemistry 1874-80 (1988) . Yet, in spite of their increased resistance to nuclease degradation, the intracellular delivery of these analogs is still poor. In addition, in an attempt to increase cellular uptake, high concentrations of inhibitory oligonucleotides have been used; however, these high concentrations may lead to nonspecific, toxic side effects. Furthermore, once internalized, the oligonucleotides may be sequestered inside the endosomal/lysosomal vacuoles, impeding their access to target mRNA molecules. Of the aforementioned methods, liposomes are potentially an excellent choice for the delivery of oligonucleotides in vivo . Liposomes are highly versatile and can be utilized to entrap both hydrophobic and hydrophilic molecules. Moreover, liposomes have been shown be readily takeup by a variety of cells and that once internalized, they are localized in the cytoplasm, allowing access of the oligonucleotides to target cells intracellularly . See Tari, A., et al., Liposome Delivery of Oligonucleotides, 21 Leukemia and Lymphoma 93-7 (1995) . 5. Administration Of Anti-Viral Agents While the subject of the preferred embodiment of the present invention is a human, other subjects which can be treated or whose tissue may be utilized includes, but is not limited to, rodent, primate, monkey, pig, horse, rabbit, dog, or cat. As used herein, the term administration is defined as a method of administering a specific agent to a subject. Such methods are well known to those skilled in the relevant arts, and include, but are limited to, administration topically, orally, subcutaneously, parenterally, intravenously, intramuscularly, intraperiteneoly, aerosol, or by other systemic forms. Those skilled in the relevant art will appreciate that the appropriate administration protocol will be dependent upon the judgment of the clinician, the specific agent utilized, and the individual subject. In addition, administration of the agent may be effected continuously or intermittently such that the chosen therapeutic agent provided to the patient/subject is effective to treat the patient/subject with a KSHV-associated disease. The chosen agent (s) are administered in a manner which is compatible with the specific dosage formulation, and in a therapeutically-effective concentration. The exact concentration of the chosen agent (s) are dependent upon both the judgment of the clinician and the particular physiology of the patient/subject. Suitable regimes for the initial administration and subsequent "booster" administrations of the chosen agent (s) are variable, but are typified by an initial administration followed by a series of repeated doses at intervals by injection or other form of administration. The pharmaceutical formulation or composition of the present invention may be in a dosage form of a solid, semi-solid, or liquid (e.g., suspensions, aerosols, or similar compositions). Preferably, the composition (s) are administered in unit-dosage form suitable for a single dosage of a precise dosage concentration. The composition (s) may also include, depending upon the desired formulation, pharmaceutically-acceptable, non-toxic, non- immunogenic carriers or diluents, which may be defined as vehicles generally utilized in the formulation of pharmaceutical compositions for human and/or animal administration. The carrier or diluent utilized is chosen so as not to affect the composition's biological activity. Examples of such diluents include, but are not limited to, dis- tilled, deionized water, physiological saline, PBS, Ringer's solution, dextrose solution, and Hank's solution. Furthermore, the pharma-ceutical composition or formulation may also include other carriers, adjuvants, or non- toxic, non-therapeutic, non-immunogenic stabilizers and the like. The effective concentrations of such diluents or carriers are those concentrations which are effective to obtain a pharmaceutically-acceptable formulation in terms of solubility of indigenous components, biological activity, side-effects, etc. B. Immunologic-Based Therapeutics Immune-based therapies may be utilized to modulate the immune dysfunction which accompanies herpesviral infection in lymphoproliferative disease such as multiple myeloma and MGUS. Specifically, agents which are capable of blocking the initial infection of the target cell or, after initial viral infection, ameliorating the progression of the disease will be utilized. Such therapies will include, but are not limited to: (1) KSHV- specific antibodies or fragments thereof which possess identical specificity (CDR fragments) which directly block the infection of the target cells, (2) KSHV-specific antibodies or fragments thereof which possess identical specificity (CDR fragments) which interact with various cellular components (e.g., cytokines or other growth regulating factors) which either modulate the replication of the virally-infected cell or which upregulate the immune system to "target" the virally-infected cell, or (3) KSHV-specific antibodies or fragments thereof which possess identical specificity (CDR fragments) to which are conjugated various anti-viral agents. The antibody may be polyclonal or monoclonal in nature and may be produced by techniques well known in the relevant fields. Polyclonal antibodies may be generated by conjugation of an antigen (e.g., selected nucleic acids, peptides, or polypeptides, or preferably a synthetic, viral-specific peptide initially produced by in vi tro translation in a mammalian cell line) to a carrier protein for use as an immunogen. The immunogen conjugate is then used to immunize an inbred strain of mouse (e.g., balb/c) using a standard adjuvant, such as Freund's adjuvant, and a standard mouse immunization protocol. See Harlow, N.C & Lane, R. , Antibodies : A Labora tory Manual (Cold Spring Harbor Press) (1988). Alternately, polyclonal antibody-containing immune globulin from individuals who have previously been infected with KSHV, or related herpesviruses, may be obtained using standard techniques. See Harlow & Lane, supra . Briefly, immune globulin preparations may be obtained from individual donors who are screened for antibodies directed against KSHV, and plasmas from high- tittered individuals may be pooled. In addition, plasmas from donors may be pooled and assayed for antibodies directed against KSHV, high-tittered pools are then selected for use in patients with KSHV-associated disease. The appropriate titers of antibody are known for this therapy and are readily applicable for the treatment of KSHV-associated diseases such as MM or MGUS. The immune globulin may be administered via parenteral injection or intrathecal shunt. Monoclonal antibodies may be obtained by various methods familiar to those skilled in the art. Briefly, spleen cells or other antibody-producing lymphocytes from an animal (e.g., mouse) immunized with the desired antigen are immortalized, generally by PEG-based fusion with a myeloma cell. See Kohler & Millstein, 6 Eur. J. Immunol . 511-9 (1976) . Alternative methods of immortalization include, but are not limited to, transformation with Epstein-Barr virus (EBV), retroviruses, oncogenes (e.g., c-myc, c-abl ) , or other similar methods. The "colonies" arising from single immortalized cell (i.e., hybridoma) are screened for the production of antibodies of the desired specificity and affinity for the antigen. The yield of the monoclonal antibodies produced by the hybridoma may be enhanced by various techniques, including injection into the peritoneal cavity of a vertebrate host. In addition, new techniques using recombinant phage antibody expression systems can also be used to generate monoclonal antibodies. See Marks, J.D., et al . , 222 J. Mol . Biol . 581-97 (1991); Hoogenboom, H.R., et al., 19 Nuc . Acids Res . 4133-42 (1991); McCafferty, J. , et al., 348 Nature 552-4 (1990) . In addition, antibody fragments, which possess indentical specificity, of KSHV-specific polyclonal or monoclonal antibodies may be utilized in any of the aformentioned manners. The antibody may be administered systemically by injection (e.g., I.M., I.V., subcutaneously, or intraperitoneally) . Typically, systemic administration of the antibody is made daily by parenteral or non-parenteral means, although administration may also be through the use of microspheres, liposomes, or similar microparticulate delivery methods. The dosage utilized will be a function of the properties of the antibody employed and will include such factors as the activity, biological half- life, class of compound, the concentration of the antibody in the for-mulation, the method and site of dosage. In addition, factors including the age, weight, and clinical condition/ tolerance of the individual patient, the specific disease afflicting the patient, the experience and judgment of the clinician or practitioner administering the therapy, etc. In addition, Generally, the antibody of the present invention will be administered in solution with a pH range of 5 to 9.5, and preferably in the physiological range of 6.5 to 7.5. The antibody, or derivative thereof, will be in a solution consisting of a pharmaceutically-acceptable buffer (e.g., Tris-HCl, PBS, etc.) in a concentration of 10 to 100 mM. The antibody solution may also contain a salt, to facilitate maintenance of the tertiary conformation of the antibody, such as sodium chloride or potassium chloride in a concentration of 50 to 150 mM. Additionally, a stabilizing agent (e.g., an albumin, a gelatin, a globulin, a protomine or salt of a protomine) may be added to the solution containing the antibody or to the solution from which the composition is prepared. Typically, the antibody may be administered singly, or in a mixture containing two or more antibodies, as well as various other therapeutic agents including, but not limited to, immunosuppressive agents, anti-viral compounds, potentiators, and agents useful in mitigating adverse side effects (e.g., agents which suppress allergic reactions in the recipient) . Immunosuppressive agents of interest include, but are not limited to, prednisone, prednisolone, cyclophosphamide, cyclosporine, 6-mercapto- purine, metho-trexate, azathioprine, gamma globulin, alone or in combination. Potentiators of interest include, but are not limited to, monensin, ammonium chloride, and chloroquine. All of these aforementioned agents are administered in pharmaceu-tically-accepted and efficacious doses as disclosed in the Physicians Desk Reference, 50th edi tion , (Barnhart, E.R., editor) (1995). C Vaccines and Other Prophylactic Therapies The present invention also provides a method of vaccinating a subject against KSHV-associated disease, comprising administering to the subject a pharmaceutically-effective dosage of a specific antigen (e.g., nucleic acid, peptide, or polypeptide) indigenous to the virus in a pharmaceutically-acceptable carrier, thereby vaccinating the subject against potential KSHV infection and its associated diseases. Therapeutic polyclonal or monoclonal antibodies may be used as a mode of passive im unotherapy of herpesvirus- induced diseases. For example, the immune globulin (containing polyclonal antibodies) , derived from individuals previously infected with KSHV or a related herpesvirus and bearing suitably high titers of antibody directed against the herpesvirus, may be utilized alone or in combination with an anti-viral agent (e.g., ganciclovir) or in combination with other modes of immunotherapy which are currently being evaluated for the treatment of other virally-induced diseases (e.g., agents which modulate the immune system such as T-cell "vaccination" ) . There are numerous techniques by which an antigen's effectiveness in eliciting an immune response may be amplified. For example, cyclization or circularization of a peptide or polypeptide can augment the molecule's antigenic and immunogenic potency. See U.S. Patent No. 5,001,049, which is incorporated herein by reference. In addition, the selected antigen may be conjugated to a suitable carrier molecule, generally a protein. This conjugation procedure has several advantages. First, it allows multiple copies of the antigen (e.g., a peptide) to be conjugated to a single, larger carrier molecule. Second, the carrier may possess properties which facilitates the transport, binding, absorption, and/or transfer of the antigen in vivo . Exemplar carriers for parenteral administration (i.e., subcutaneous injection) include tetanus toxoid, serum albumin, diphtheria toxin, and lamprey or keyhole limpet hemocyanin — as they provide the resultant conjugate with minimal genetic restrictions. Moreover, conjugates which utilize these universal carriers can function as T-cell clone activators in individuals possessing very different gene-sets. The conjugation of the antigen to the carrier molecule may be accomplished by use of one of the methods known in the art. For example, the conjugation can utilize bifunctional cross-linkers as binding agents. See Means, J. & Feeney N.B., A Recent Review of Protein Modification techniques, 1 Bioconj uga te Chem . 2-12 (1990). The chosen antigen may be combined or mixed with various solutions and/or other compounds known in the art. For example, it may be administered in water, saline, or buffered solutions with or without the addition of various adjuvants or immunodiluting agents. Examples of adjuvants or immunodiluting agents include, but are not limited to, aluminum hydroxide, aluminum phosphate, aluminum potassium sulfate (alum) , beryllium sulfate, silica, kaolin, carbon, water-in-oil emulsion, oil-in-water emulsion, muramyl dipeptide, bacterial endotoxin, lipid X, Corynebacterium parvum, Bordetella pertussis , polyribonucelotides, sodium alginate, lanolin, lysolecithin, vitamin A, saponin, liposomes, levamisole, DEAE-dextran, blocked copolymers, or other synthetic adjuvants. Many of the aforementioned adjuvants are commercially available from Merck Adjuvant 65 (Merck & Co., Inc., Rahway, NJ) or Freund's Incomplete and Complete Adjuvant (Difico Laboratories, Detroit, MN) . Vaccines directed against KSHV may, for example, be produced by the initial isolation of extracellular viral particles from a lytically-infected in vitro cell culture of BMSCs. The virus is then inactivated by heat or formaldehyde treatment, followed by ultracentifugation to collect the viral particles and remove the formaldehyde. The individual may by inoculated with 2-3 doses of approximately 1 x 10 9 viral particles. See Skinner, G.R., et al., 14 Comp. Immuno . Microbiol . Infect . Dis . 13-22 (1991) . Alternately, viral envelope glycoproteins can be expressed in E. coli or transfected in stable mammalian cell lines in vi tro, and the expressed proteins may be purified and used for vaccination. See Lasky, L.A., 31 J. Med. Virol . 59-71 (1991). A recent study has also demonstrated that MCH-binding peptides from cells infected with KSHV can be identified for vaccine candidates. See Marloes, J.D., et al., 21 Eur. J. Immunol . 2963-70 (1991). 1. Kshv Vaccine Constructs The following sections will discuss the various types of constructs which may be utilized to develop a therapeutically-effective KSHV vaccine for human use. Vaccines may be based upon immunization with various forms of antigenic material (e.g., recombinant proteins developed from proteins present in the viral envelope) which directly elicits an antibody-based immune response or, alternately, with material which results in the expression of an antigen (e.g., recombinant virus). These two viral vaccine developement methods will be referred to as non-expression-based and expression-based vaccines, respectively, and will be fully discussed in subsequent, separate sections. 2. Non-Expression-Based Vaccines Non-expression-based vaccines include those vaccines which do not rely on in vivo expression of the immunogenic material (i.e., material which produces an immune response) . Various types of immunogenic materials include: whole killed or attenuated virus, native-like viral proteins, non-native-like viral proteins, recombinantly engineered proteins or peptides, and various super-molecular assemblies containing several viral envelope proteins or peptides. a. Whole Killed Virus The primary attraction of utilizing whole killed virus as an KSHV vaccine is that, in theory, it includes the entire collection of viral proteins in a structural form which directly mimics the natural infecting virus. In practice, whole killed vaccines have been relatively efficacious in the past and numerous vaccines have been developed using this method. Although whole killed virus vaccines have shown protection against infection from a challenge with naturally occurring virus in Simian Immunodeficiency Virus (SIV) vaccine trials, the observed protection could have potentially been derived from a simian antibody response to the human cell-associated antigens present in both the immunogen and the secondary viral challenge. See Desrosiers, R.C et al . , Vaccine Protection Against Simian Immunodeficiency Virus Infection, 86 Proc. Na tl . Acad. Sci . 6353-7 (1989). Conversely, when simian cell-associated antigens were utilized, no such antibody-mediated protective response was noted. See Murphy-Corb, M. et al., A Formalin- Inactivated Whole SIV Vaccine Confers Protection to Macaques, 246 Science 1293-5 (1989). b. Native-Like Viral Proteins The term native-like viral protein refers to native viral protein purified from the virus or virally-infected cells, or to relatively authentic recombinant forms of these proteins. Native-like proteins limit the immune response to specific proteins of interest and exclude others. This utilization of specific viral proteins assumes knowledge of the optimal protein "targets" for eliciting immune response. When selecting native and/or developing recombinant viral proteins one must be acutely aware of maintaining the three-dimensional conformation of the specific protein, for it is this structural orientation which elicits the proper immune response. c. Non-Native Proteins As the nomenclature implies, non-native proteins are those which have somehow been altered such that they no longer possess the unique, specific structural characteristics of the naturally-occurring viral protein. For example, absent or altered glycosylation may make a viral protein relatively non-native, and thus unable to elicit an immune response. Protein denaturation (alteration of a protein's specific and highly conserved three-dimensional structure) may also destroy the protein's native structure. In addition, recombinant proteins are often expressed in non-mammalian cells (e.g., bacterial or yeast) due to the ability of these cells to "secrete" the desired protein into the fluid growth medium, thus making protein isolation and purification easier. Unfortunately, proteins expressed in these cells may also possess intrinsic differences from those expressed in mammalian systems and may be considered to be non-native. While the native forms of viral proteins appear optimal for eliciting antibody-mediated immune response, the subtly, or even grossly, non-native conformations of these proteins may also offer special utility in vaccine developement . For example, a denatured viral protein may potentially be used to generate a desired cellular response, without eliciting an antibody response to these non-native conformation proteins. Denaturation may also, in some cases, obviate antigen processing, thereby minimizing dependency on accessory cells such as T-lymphocytes . For example, however, several recent studies have shown that the processes of denaturation, degly-cosylation, alkylation, and reduction do not con-sistently enhance immunogenicity of the gpl60 envelope protein of HIV in either T-cell or antibody responses when used alone, or in concert with non- denatured gpl60 protein. See e.g., Belshe, R.B. et al . , Safety and Immunogenicity of a Human Immunodeficiency Virus Type I (HIV-1) Recombinant gpl60 Candidate Vaccine in Humans, NIAID AIDS Vaccine Clinical Trials Network, 114 Ann . Intern . Med. 119-34 (1991). d. Recombinantly-Engineered Proteins Recombinantly-engineered proteins typically abandon native structure in favor of novel conformations specifically designed to elicit maximal immune responses with the desired characteristics. Such designs generally arise from specific structure-biological activity concepts, practical considera-tions, and/or a combination of the two. A major value of such constructs are that they may be designed to avoid induc-tion of immune responses which might contribute to immune deficiency or viral enhancement. Larger recombinantly-engineered constructs which represent a major portion of the target native viral protein may adequately represent such native conformations. See Straus, S.E. et al., Induction and Enhancement of Immune Responses to Herpes Simplex Virus Type 2 in Humans by use of a Recombinant Glycoprotein D Vaccine, 167 J. Infect . Dis . 1045-51 (1993) . Conversely, smaller peptide constructs typically lack stable conformations, but nonetheless may elicit an immune response which produces antibodies which demonstrate cross-reactivity with native proteins. Because T-lymphocytes recognize only processed antigens which generally lack native conformation, recombinantly-engineered proteins are especially well suited for use in vaccines designed to elicit T-cell, rather than B-cell antibody, response. In principle, these constructs offer complete control over the overall focus of the immune response. However, inclusion of a specific domain (region) indigenous to the native envelope protein in an engineered construct does not guarantee its efficient function as a immunogenic agent. e . Super-Molecular Assemblies Several research groups have developed strategies for developing larger protein assemblies containing copies of one or more epitopes, or regions of proteins which are effective in eliciting an immune response. See Fast, P.E., & Walker, M.C, Human Trials of Experimental AIDS Vaccines, 9 (Suppl. 1) AIDS 71-94 (1993). Rather than "fusing" the viral protein epitope of interest to a single T-cell protein, the rational in this method is to "fuse" the epitope to a larger, highly immunogenic protein which, in effect, functions as a carrier protein. Selection of a specific fusion "partner" may result in the formation of protein particulate. A number of conceptually similar particulate immunogen constructs have been developed for viral proteins including proteins which range in size from a single epitope to full-size native proteins. These constructs are currently being utilized in initial-stage clinical trials. See Hoff, R. et al . , Monitoring Immunogenicity and Infection in HIV Vaccine Efficacy Trials, 9 (Suppl. 1) AIDS 147-57 (1993). Additionally, for synthetic peptide constructs, lipid molecules can be attached to the protein structure to facilitate incorporation into a lipid-based (or fat-soluble) carrier matrix. This lipid attachment has the advantages of providing both the ability to deliver the immunogenic complex via intramuscular steady-state delivery and allowing the immunogen to interact with the various proteins associated with the lipid-based cell membrane in a highly efficacious manner. 3. Expression-Based Vaccines The highly celebrated success of Jenner's use of the closely-related vaccinia virus to eradicate smallpox attests to the valuable potential of expression-based vaccines. The use of a live related virus as the vaccinating agent has given way to the utilization of the live pathogenic virus itself, although in a weakened or attenuated form. Over the past decade, this class of vaccines has been augmented by a diversity of recombinant viruses and bacteria, as well as by more direct gene transfer and genetic immunization strategies. In the following section, it is helpful to further differentiate expression-based vaccine systems as a function of their ability, or non-ability, to replicate progeny virus which enables transmission to other cells. a. Replicating (1) Attenuated Live Virus In the early years of the AIDS epidemic, an attenuated live virus vaccine for KSHV for use in a preventative or even therapeutic role was discounted primarily due to safety concerns. However, recent findings by several research groups utilizing the closely- related Simian Immunodeficiency Virus (SIV) , has prompted reconsideration of this method. Recent data has shown that the injection of live SIV, modified in a manner which reduced its virulence, elicited an antibody-mediated immune response which provided protection against a subsequent challenge of non-attenuated SIV. See Murphy- Corb, M. et al., A Formalin-Inactivated Whole SIV Vaccine Confers Protection to Macaques, 246 Science 1293-5 (1989) . While this immune response did not entirely eliminate SIV infection, it did greatly delay the onset of disease following a massive intravenous administration of non- attenuated SIV. Both the type and degree of immunological protection appears to be highly dependent upon the specific manner which is utilized to generate the attenuated virus. A major caveat for this type of approach is the demonstrated prolonged persistence of the attenuated virus within the "infected" animals which raises serious safety considerations. (2) Recombinant Viruses Recombinant vaccinia virus, a virus closely related to the small pox virus, is currently being studies as a "vehicle" or vector for the delivery of viral envelope protein (s) as a potential vaccine. Because the vaccinia virus contains a relatively large genome (genetic material) , it can accommodate several heterologous genes of interest from other viral sources. For example, recombinant vaccinia virus expressing one or more viral envelope proteins (e.g., env, pol , gag ) were among the prototype vaccine constructs to be developed for HIV. See Cooney, E.L. et al., Safety and Immunological Response to a Recombinant Vaccinia Virus Vaccine Expressing HIV Envelope Glycoproteins, 337 Lancet 567-9 (1991) . In initial studies, these constructs elicited antibody- mediated immune responses which provided varying degrees of protection against HIV infection in primates. It should be noted that there is some concern that vaccine regimens involving recombinant vaccinia may be hazardous for immunocompromised individuals. This concern has prompted the development of alternative recombinant viral vectors . Attenuated live adenovirus vaccines were initially developed in the late-1970's for use in high-risk populations. See Serwandda, D. et al., Immunization of High Risk Population in Uganda with a Live Attenuated Adenovirus Subgroup B Strain, 98 J. Infect . Dis . 872-7 (1973). The extensive clinical experience which has been amassed for adenovirus make them attractive viruses from which to develop recombinant vaccines. While the viral genome of adenovirus is smaller than that of vaccinia virus, it is still capable of accommodating one or more full-length viral envelope protein genes which may be of interest. Several recombinant adenovirus constructs containing HIV envelope protein genes (e.g., the env gene) have been developed which show promise in eliciting a protective immune response against HIV infection. See Fast, P.E., & Walker, M.C, Human Trials of Experimental AIDS Vaccines, 7 (Suppl. 1) AIDS 147-54 (1993). One potential difficulty which may be encountered is the constraints placed upon animal test models due to the limited host range of human adenovirus. Safety, efficacy, and the ability to elicit immunity argue for the use of the poliovirus as a vector for recombinant vaccines. Recombinant poliovirus constructs have been demonstrated to possess some ability to elicit a protective immune response; although these are not nearly as effective as the other two types of viral constructs utilizing vaccinia and adenovirus. See WHO Working Group, Feasibility of Developing Live Attenuated KSHV Vaccines: Conclusions and Recommendations, 10 AIDS 221-44 (1994). (3) Recombinant Bacteria As the technical barriers to the generation of chromosome- or plasmid-based recombinant bacteria have been overcome, recombinant bacterial strains may be utilized as a vector in the development of an KSHV vaccine. For example, recombinant bacterial strains have been developed for Mycobacterium bovis and Salmonella typhimurium which expressed HIV proteins such as gag, pol , ta t , and env. These bacterial constructs were shown to elicit both antibody and cellular immune responses in murine (mouse) models. See Fuxman, Y.S. et al., Recombinant Mycobacterium bovis and Salmonella typhimurium expressing Human Immunodeficiency Virus Type I (HIV-1) Envelope Proteins, 53 J. Bacteriol . 592-613 (1992). The localization of the expressed protein (serving as an antigen to induce an immune response) appeared to be a critical determinant of the immune response to the recombinant bacterial species, with expression on the outer surface of the bacterial cell membrane in the form of an membrane-anchored fusion protein appearing optimal for eliciting humoral responses. Interestingly, constructs utilizing Salmonella typhimurium (a bacteria which causes the common food-poisoning Salmonella) expressing the HIV env protein was demonstrated to generate an identifiable antibody-mediated immune response following oral administration in murine models. See Mattmuller, L.V. et al . , Oral Administration of Salmonella Typhimurium expressing the Human Immunodeficiency Virus Env Protein Strongly Stimulates Antibody Production, 116 J. Infect . Dis . 981-7 (1992). b. Non-Replicating A number of constructs have been developed that enable the delivery and subsequent expression of various viral genes of interest but without the replication of a transmissible agent (i.e., an infective progeny virus) in vivo . Such constructs are often far less complex than the replicating constructs and may offer several safety advantages, especially in immunocompromised individuals. (1) Avipox Viruses The avipox viruses, canary pox, and fowl pox viruses infect mammalian cells in a manner which results in efficient protein expression but does not lead to viral production. This has provided a basis for developing avipox-based vaccine constructs for measles, influenza, rabis, and SIV. See Mazzara, G.P. et al . , Development of Constructs Utilizing Avipox Virus and Simian Immunodeficiency Virus Envelope Proteins, 67 Cell 653-8 (1992) . (2) Retroviral Vectors Retroviral gene transfer vectors have recently been developed which elicit both antibody-and cellular-mediated responses specific for the HIV env protein in murine models. See Stanhope, et al . Human Retroviral CD4 Constructs Elicit Immune Responses Via a Glycoprotein gpl60-Specific Immune Response, 150 J. Immunol . 168 (1993); Hammond, S.A. et al., Characterization of a Conserved Epitope in HIV-I gp41 and gpl20 Envelope Proteins Recognized by Retroviral Vaccine-Induced Cytolytic T-Cells, 146 J. Immunol . 1470-6 (1993). The cellular-mediated immune response was especially interesting in that the activated T 8 - (killer) lymphocytes exhibited a broad range of specificity to cells infected with various strains of HIV. This type of cross- reactivity with multiple viral strains is important, for it allows a single type of vaccine to be utilized due to its polyvalent nature. (3) Genetic Immunization All of the aforementioned expression-based strategies have taken advantage of modified viruses or bacteria to achieve efficient gene expression in vivo . However, it appears that immunogenic levels of expression can be achieved with direct injection of an appropriate expression construct — a process known as "naked" DNA or genetic immunization. The potential efficacy of this technique was demonstrated by a research group which elicited influenza virus nucleoprotein-specific cellular immunity which protected mice from an influenza challenge with a heterologous influenza strain, thus demonstrating viral strain cross-reactivity. Similarly, direct immunization with influenza hemagglutinin-expressing constructs has also been shown to elicit influenza protection in chickens and mice. See Ulmen, P.E. et al . , Genetic Immunization with Influenza Strain RT-3A Nucleoprotein-Specific DNA Produces an Immune Response in Murine Systems and Effectively Protects Against Heterologous Influenza Challenge, 146 J. Immunol . 491-7 (1992) . Most recently, researchers have explored this approach using an HIV gpl60 protein expressing construct which elicited significant antibody responses including virus-neutralizing activity. See Warren, R.Q. et al . , Synthetic Peptides Define the Fine Specificity of the Human Immunodeficiency Virus (HIV) gpl60 Humoral Immune Response in KSHV Type I-Infected Chimpanzees, 64 J. Virol . 486-9 (1991) . 4. Vaccine Formulation And Protocol Issues Non-expression-based vaccines are generally less immunogenic in nature than the replicating, expression- based vaccines, in the absence of a strong adjuvant. See La Valle, T.R., Adjuvant Development and Immunization Strategies. In : Vaccines ' 92 : Modern Approaches to New Vaccines Including Prevention of AIDS. Cold Spring Harbor Press, New York (Lerner, R.A. , Ginsberg, H., and Brown, F., eds. 1993). Consequently, optimal adjuvant formulation is essential to maximize the efficacy of the immunogenic agent in eliciting a vigorous response. The use of alum is the only adjuvant formulation currently in general clinical use in the United States. Alum-based adjuvant formulations have been reported to favor Th2-like responses, whereas complete Freund's adjuvant may favor Thl-like immune responses. The mycobacterial antigenic components present in complete Freund's adjuvant, like that of recombinant malarial proteins, appear to be primarily responsible for the Thl-like responses which are elicited. Future identification of these Thl responses to these antigens should potentially lead to more selective adjuvant development and selection. It has recently been shown that it is possible to elicit cytolytic (cell killing) responses from the CD 8-expressing T 8 (killer) lymphocytes by the use of HIV-specific core and/or envelope proteins in highly specialized adjuvants such as ISCOM. See Guyner, M.P. et al., Potentiation of the Protective Effects of Human Immunodeficiency Virus Envelope Protein or Core Protein-Based Immunization by Utilization of ISCOM Adjuvant Systems, 12 EMBO J. 6581-7 (1993). Indeed peptide immunization has produced protection against other viruses and intracellular bacteria in several recent animal studies. See Gendelmann. K.T. et al., The Development and Utilization of Synthetic HIV-Specific Peptides in the Production of Anti-Viral and Anti-Bacterial Antibodies, 557 Ann . Rev. Microbiol . Immunol . 2765-87 (1992). These new types of formulations and approaches may make feasible the induction of all classes of immune response with non- expression-based vaccine constructs. In addition to the importance of adjuvant formulation, recent studies the demonstrated that the presence or absence of immunomodulators at the time of immunization can dramatically alter the type of Th-like response. For KSHV immunization, it may be more efficient to induce a Thl-like response, or the absence of a Th2- like response, at the time of initial immunization. To carry out this type of approach, one could co-administer of cytokines or anti-cytokine antibodies which would ensure the desired type of immune response. Combinations of these agents may be warranted in the setting of post- exposure to KSHV or early seropositive vaccination, where an undesirable cytokine pattern may already exist in the individual's immune system. While many of these agents must be delivered parenterally (i.e., via injection), it may be far more efficacious, especially in non- industrialized third-world countries, to develop an oral method of delivery. Recent advances in vaccine technology have lead to the development of several orally administered agents which play a role in conditioning the patient, before actual immunization, where a specific type of Th response is sought or for maintaining a state that favors such a response type. One example of these immunomodulatory agents is pentoxyphilline, which has been shown to quantitatively lower levels of cyclic adenosine monophosphate (cAMP) and interleukin-11 (IL-11) . See Antoni, B.A., Cytokine Regulation of Human Immunodeficiency Virus Infection: Implications for Pathogenesis, 43 Adv. Vir. Res . 53-61 (1994). For example, the reduction of cAMP levels has been demonstrated to normalize T-lymphocyte function in HIV- infected individuals. See Clouse, K.A. et al., Monokine Regulation of HIV-1 Expression in a Chronically Infected Human T-Cell Clone, 142 «J. Immunol . 431-9 (1990). Additionally, several non-steroidal anti-inflammatory drugs (NSAIDS) have been shown to possess the ability to block the production of prostaglandin-E 2 (PGE 2 ) in macrophages, which, in turn, selectively blocks production of IL-2 and interferon-gamma (IFN-D) in T-lymphocytes. See Francis, M.L. et al., Interferons in the Persistence, Pathogenesis, and Treatment of HIV Infection, 8 AIDS 199- 207 (1992); Meylan, P.R. et al., Mechanisms for the Inhibition of HIV Replication by Interferons Alpha-, Beta- , and Gamma in Primary Human T-Cell and Macrophage Cultures, 193 Virology 138-45 (1993). Therefore, oral agents such as pentoxyphilline and NSAIDS merit evaluation for use in a conditioning regimen prior to, or maintenance regimen following, initial vaccination. A third element in effective vaccination is the dose of antigen administered to elicit an immune response. The antigen dose has been found to be a determinant of the specific type of T response elicited. For example, low- dose immunization was demonstrated to possess the ability to induce delayed hypersensitivity (a Thl-like response) without antibody production or response (a reflection of a Th2-like response) . Thus, low-dose immunization may represent a simple strategy for inducing Thl-like responses without concomitant antibody activation and/or production. Conclusion Prior to the present invention disclosed herein, KSHV-specific sequences have not been demonstrated in two monoclonal lymphoproliferative disorders — multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) . These KSHV-specific sequences have herein been demonstrated to be associated with only the non-malignant bone marrow stromal cells (BMSCs) , suggesting that KSHV may promote MM oncogenesis by selectively infecting these BMSCs. Hence, this is the first report that KSHV may directly support the growth of a hematologic malignancy by infecting a non-malignant cell without infecting the malignant clone. In addition, the KSHV genome has been shown to contain a viral IL-6 homolog (vIL-6) . Transcripts of vIL-6 have been demonstrated to be encoded by BMSCs in MM patients, and vIL-6 plays an important role as a growth factor in this disease. More specifically, in MM, BMSCs have been shown to produce large quantities of IL-6, which serves to stimulate growth/proliferation and prevents apoptosis of the malignant plasma cells in a paracrine manner. For the role of IL-6 in cells, see Anderson, K.C, et al., 73 Blood 1266-72 (1989); Lichtenstein, A., et al., 73 Blood 248-56 (1989); Hirano, T., et al., 9 Int . J. Cell Cloning 166-71 (1991); Kishimoto, T., et al., 258 Science 593-5 (1992); Uchiyama, H., et al., 82 Blood 3712- 9 (1993) . As shown in the examples (see Figure 2), KSHV- specific sequences were found in the BMSCs of MM patients, but not in the malignant plasma cells from these same patients. Similarly, KSHV-specific sequences were not detected in either the BMSCs of "normal" individuals (i.e., donors for allogenic transplants) or BMSCs of patients with other hematological malignancies. These KSHV-specific sequences were cloned and sequenced, thus confirming their homology to KSHV (see Figure 3) . Moreover, in si tu hybridization results established that the vIL-6 was expressed by the cultured BMSCs of MM patients, rather than by the malignant myeloma cells themselves (see Figure 4). In si tu hybridization also showed that KSHV was present in fresh BMSCs from bone marrow biopsies. Further, KSHV was detected by PCR in circulating dendritic cells from the peripheral blood of MM patients, in addition to cultured BMSCs from MM patients. Hence, it may be concluded from these results that KSHV promotes the development of MM by the direct infection of dendritic cells. In addition, KSHV-specific sequences were also detected in the BMSCs of 4 of 15 MGUS patients. As previously discussed, MGUS is characterized by the presence of a monoclonal immunoglobulin in the serum and an increase in monoclonal plasma cells in the BM. MGUS patients do not, however, suffer the other clinical manifestations of MM such as increased risk of infection and lytic bone lesions. Most importantly, recent studies have demonstrated that approximately 25% of MGUS patients will subsequently develop some type of malignant hematological disease (e.g., MM). Hence, the detection of KSHV-specific sequences in the BMSCs of MM patients cannot be explained only by the unique immunologic state due to the generalized suppression of immunoglobulin production in multiple myeloma. Experimental results have also demonstrated that KSHV does not appear to infect BM cells other than stromal cells (BMSCs) . Electron microscopic ultrastructural studies showed these cells to contain abundant cytoplasm with numerous lysosomal granules, vacuoles, and short cytoplasmic processes. In situ hybridization with a KSHV- specific biotinylated probe [see Figure 1, SEQ ID No. 3b] demonstrated that the viral DNA was present in both the nuclear and cytoplasmic regions. In addition, immunohistochemical staining with a macrophage-specific CD68 marker, resulted in a high degree of binding on BMSCs. In contrast, an endothelial cell-specific CD31 marker was negative on BMSCs [see Figure 5, panel d] . Therefore, based upon these findings, the BMSCs which KSHV appears to infect are macrophages, rather than the B- lymphocytes or endothelial cells which are also present in the bone marrow microenvironment . Increases in both the amplification and detection of the KSHV sequences have also allowed the viral-specific sequences to be demonstrated in BMMCs as well as in the isolated BMSCs. Accordingly, this allows for more rapid detection of KSHV sequences as the requirement for BMSC isolation is mitigated. In conclusion, the findings disclosed in this application indicate that, in patients with MM and MGUS, KSHV specifically infects a non-malignant cell, namely the BMSC. In doing so, KSHV is localized to the BM microenviroment where viral genes (e.g., vIL-6) are expressed and may support MM growth. In contrast, the BMSCs of "normal," non-Hodgkin' s lymphoma (NHL), and Hodgkin's disease (HD) patients were consistently negative for the presence of KSHV. Taken together, this data suggests that KSHV may promote MM oncogenesis by specifically infecting BMSCs. Most importantly, the discovery described herein represents the first report that KSHV appears to directly support the growth of a hematologic malignancy by infecting a non-malignant cell without infecting the malignant clone. As a result of this discovery, the present invention was made possible. It is now possible to detect the presence or absence of KSHV in MM and MGUS patients as a means for diagnosing MM. It is also now possible to treat MM by treating the KSHV infection, and to prevent the development of MM through prophylactic treatment aimed at prevention or elimination of KSHV infection. Further, it may be possible to diagnose those MGUS patients whose disease will develop into MM, and to prevent the development of MM in those patients by anti-KSHV treatment. EXAMPLES The following section will disclose one set of experimental methods utilized in the present invention. While these methods were primarily applied to KSHV- associated diseases of a lymphoproliferative nature (e.g., MM and MGUS) , they could equally well be applied to the study of other malignant and non-malignant disorders including, but not limited to, autoimmune (e.g., SLE, rheumatoid arthritis, etc.) or neurological (e.g., Alzheimer's disease, multiple sclerosis, etc.) diseases. Further, the methods of this invention are not limited to the specific techniques described herein, but include other methods known in the field. EXAMPLE 1 PATIENT MATERIAL Bone marrow (BM) aspirate specimens were obtained from a total of 19 patients with active multiple myeloma (MM) , 6 "normal" donors for allogenic BM transplantation, 6 non-Hodgkin' s lymphoma (NHL) patients, and 2 Hodgkin's disease (HD) patients. All specimens were obtained following informed consent and in compliance with the Human Subjects Protection Committee. Cytospins of MM bone marrow mononuclear cells (BMMCs) , which were separated by HISTOPAQUE ® (Sigma Pharmaceuticals) density sedimentation, demonstrated 11-90% malignant plasma cells in all cases. Peripheral blood from myeloma patients, MGUS patients, patients with other hematologic malignancies, and normal individuals (60 ml/patient) was collected in heparinized tubes after informed consent and in accordance with Human Subjects Protection Committee. Whole blood specimens were diluted 1:1 with Leibovitz L-15 medium (GIBCO/BRL, Grand Island, NY) supplemented with bovine serum (L-15/FBS, GIBCO/BRL) . The peripheral blood mononuclear cell fraction was obtained by density sedimentation on Ficoll-Hypaque (Pharmacia, Upsala, Sweden) at 600 x g for 20 min and washed twice in L-15/FBS media. Five million mononuclear cells were used to extract DNA with the Easy DNA kit (Invitrogen, San Diego, CA) per the manufacturer's instructions. The remainder of the mononuclear cell fraction was used to enrich for macrophage/ dendritic cell markers (see below) . DNA was quantified on a DyNA Quant 200 fluorometer (Hoefer Pharmacia Biotech, San Francisco, CA) EXAMPLE 2 IN VITRO CULTURE OF BMMCS AND BMSCS FROM MM PATIENTS Bone marrow mononuclear cells (BMMCs) were initially separated by Ficoll-Hypaque density sedimentation and utilized in the establishment of long-term in vi tro cultures of bone marrow stromal cells (BMSCs) as previously described. See Gartner, S.M., & Kaplan, H.S., 77 Proc . Na t ' l Acad. Sci . 4756-61 (1980), whose disclosure is incorporated herein by reference. Specifically, BMMCs were suspended in -10 ml of Iscove's modified Dulbecco ' s medium (Irvine Scientific) supplemented with 10% fetal calf serum (Gemini Bio-Products), 200 mM L-glutamine (Gemini Bio-products), and lOOμg/ml streptomycin (Irvine Scientific) in a 25 cm 2 culture flask (Costar) . The cells were cultured in a C0 2 incubator at 37°C with a 5% C0 2 environment. The Dulbecco' s growth medium was changed every week. Once a confluent, adherent cell monolayer had developed, the monolayer was washed 3-times with phosphate-buffed saline, pH 7.0 (PBS, Irvine Scientific). The adherent BMSCs were removed from the culture vessel by trypsinization with 0.5% trypsin in Hanks' Buffered Saline Solution (Irvine Scientific), followed by washing in PBS. The suspended cells were collected via centrifugation. EXAMPLE 3 ISOLATION OF MM BMMC AND BMSC GENOMIC DNA The BMMCs or BMSCs were lysed according to a rapid DNA extraction procedure. See e.g., Monini, P., Kaposi's Sarcoma-Associated Herpesvirus DNA Sequences in Prostate Tissue and Human Semen, 334 New Engl . J. Med. 1168-72 (1996), whose disclosure is incorporated herein by reference. Specifically, the isolated cells were suspended in a solution containing 10 mM Tris-HCl (pH 8.0), 1% (V/V) polyoxyethylene lauryl ether, and proteinase K at a concentration of lOOμg/ml to facilitate cell lysis. The lysed cells were then incubated in the solution at 65 C for 2 hours, followed by boiling for 10 minutes. Genomic DNA was isolated from the lysed cells by extraction 3- times with phenol/chloroform/isoamyl alcohol (49:49:2 v/v/v) , 2-times with chloroform/isoamyl alcohol (98:2 v/v), and 2-times with anhydrous diethyl ether. Following extraction, the resultant genomic DNA was ethanol precipitated in the presence of 0.3 M sodium acetate pH 5.0 and collected via high-speed centrifugation. EXAMPLE 4 PCR AMPLIFICATION OF MM BMSC DNA AND SOUTHERN BLOTTING OF AMPLIFICATION PRODUCTS Polymerase chain reaction (PCR) amplification was performed utilizing genomic DNA isolated from bone marrow mononuclear cells (BMMCs), the component of bone marrow which contains the malignant cells in multiple myeloma (MM) or genomic DNA isolated from bone marrow stromal cells (BMSCs) . Patients were either Durie-Salmon stage II or III. All bone marrow aspirate specimens were obtained from the afore-mentioned patients after informed consent and in full compliance with the Human Subjects Protection Committee . Cytospins of BMMCs, which were initially separated by HISTOPAQUE ® density sedimentation, were shown to consist of > 11% malignant plasma cells cells. Genomic DNA from BMMCs and BMSCs was isolated as described in the previous section. PCR amplification was performed on the genomic DNA samples in order to detect the KS330 233 sequence as previously described. See Chang, Y., et al., Identification of Herpesvirus-Like DNA Sequences in AIDS- Associated Kaposi's Sarcoma, 266 Science 1865-9 (1994), whose disclosure is incorporated herein by reference. KS330 233 consists of a 233 bp sub-fragment of the KS330Ba.m sequence — a 330 bp sequence derived from a genomic DNA library of Kaposi's sarcoma tissue possessing 51% amino acid homology to a portion of the ORF26 reading frame encoding the capsid protein VP23 of Herpesvirus saimiri and 39% amino acid homology to the corresponding BDLFl ORF of EBV. Each PCR amplification reaction utilized approximately lμg of genomic DNA and 5 pmol of both the sense and anti-sense primers consisting of two 30 nt. oligomers possessing the sequences: 5'-TTGCAGCAGCTGTTGGTGTACCACATCTACT-3' [SEQ ID No. 1, Sense] 5'-AGTAGATGTGGTACACCAACAGCTGCTGCA-3' [SEQ ID No. 2, Anti-Sense] To the reaction mixture was also added 2.5 Units of Taq polymerase (Perkin Elmer) ; 200μm of each deoxynucleotide triphosphate; lOμl of 5X Reaction Buffer C (Invitrogen; containing: 1.5 mM magnesium chloride, 50 mM potassium chloride, 10 mM Tris-HCl (pH 9.0), and 0.1% Triton X-100); and PCR water (Invitrogen) to a final total volume of 50μl. The typical PCR reaction conditions consisted of, but were not limited to, 60 cycles of amplification performed in a programmable thermo-cycler (MJ Research) consisting of: Step 1 — 95°C denaturation step for 1 minute. Step 2 — 94°C for 1 minute. Step 3 — 58°C for 1 minute. Step 4 — 72°C for 1 minute and 30 seconds. Step 5 — Steps 2-4 are repeated for 54 cycles. Step 6 — 72°C final elongation step for 5 minutes. Although BMSCs are derived from the original BMMC population, they comprise a minute fraction of the total BM cellular component. Moreover, BM aspirates are frequently heavily contaminated with peripheral blood, a phenomenon which greatly dilutes the frequency of BMSCs in fresh samples. Consequently, while PCR amplification was capable of detecting KSHV-specific sequences in genomic DNA samples obtained from a population enriched for BMSCs, the assay did not possess the requisite degree of sensitivity to detect KSHV-specific sequences in 100 ng of genomic DNA obtained from fresh BMMCs. It should be noted, however, that KSHV must be present in the BMMCs, as the KSHV-containing BMSCs were initially cultured from the BMMCs . Thus, in order to detect KSHV-specific sequences in BMMCs which had not undergone enrichment for BMSCs in vi tro, the amount of genomic DNA from BMMCs in each PCR amplification reaction was increased from 100 ng to lDg. In addition, the total number of amplification cycles was augmented from 45 to 60 cycles. These optimizing procedures allowed the detection of KSHV-specific sequences in fresh, non-enriched BMMCs from all patients studied. Removal of the previously required step of enrichment for BMSCs serves to greatly simplify the assay. Following amplification, approximately lOμl of each of the KS330 233 amplified PCR products was subjected to electrophoresis utilizing a 1% agarose gel. Positive control for the KS330 233 amplified products was provided by genomic DNA isolated from the KS-1 PEL cell line, with placental DNA (Sigma Pharmaceuticals) serving as a negative control. Ethidium bromide was utilized to visualize the nucleic acid after electrophoresis. Following electrophoresis, the PCR products were prepared for Southern blotting. The agarose gels were inverted and the nucleic acids transferred overnight, via capillary action, to a charged nylon membrane (Scheichter & Schuell) in a high-salt solution (20X SSC) . Following capillary transfer, the nylon membrane was washed with 2X SSC and allowed to dry. The DNA was immobilized to the nylon membrane by exposure to U.V. light (230 nm) . Pre-hybridization was performed for at least 2 hours at 42°C in a solution containing 5X Denhardt ' s solution, lOOμg/ml denatured salmon sperm DNA, 5X SSC, and 1% SDS. Hybridization was performed overnight at 42°C in the same solution as the previous pre-hybridization reaction using a probe concentration of 5 ng/ml hybridization solution. The probe consisted of a 30 nt. oligomer internal to the KS330 233 sequence possessing the following sequence: 5'-TATGTTACGCCAAGCTTGGTACCGAGCTCT-3' [SEQ ID No. 3a, Sense] initially described by Chang, Y., et al., 266 Science 1865 (1994), supra . The probe was end-labeled with [γ- 32 P] deoxycytidine triphosphate, by a 4 bp extension with the Klenow fragment of DNA polymerase I (New England Biolabs) . The template for this extension was an oligonucieotide which was complementary to, and 4 bp longer (at its 5' terminus) than the probe. The extension reaction was performed at 30°C for 20 minutes. Alternately, a biotinylated internal 30 nt . oligomer could be utilized instead of a radiolabeled probe to visualize the PCR amplification products on the nylon membrane. PCR amplification of the KSHV-derived KS330 233 sequence was utilized to evaluate multiple myeloma bone marrow mononuclear cell (MM BMMC) genomic DNA and multiple myeloma bone marrow stromal cell (MM BMSC) genomic DNA for the presence of the aforementioned amplification product. A primer set specific for the KS330 233 sequence was utilized in the PCR amplification reaction [See Figure 1, SEQ ID No. 1 and No. 2]. As illustrated in Figure 2 panels a & b, KS330 233 sequences were detected in 11 of 11 MM BMSC DNA samples, whereas 0 of 19 fresh MM BMMC DNA samples yielded positive results for the KS330 233 sequence. In order to confirm the accuracy and specificity of these results, BMSC DNA was evaluated from both "normal" patients (i.e., those with no hematologic malignancies) and from patients with other types of hematologic malignancies utilizing the PCR amplification of the KS330 233 viral sequence. The KS330 233 amplification product was not able to be detected in BMSC DNA isolated from 6 "normal," 2 Hodgkin's disease, or 6 non-Hodgkin' s lymphoma (NHL) patients. Three of the six NHL patients exhibited gross BM involvement. It should be noted, that the lack of detection of the KS330 233 PCR amplification product was not due to degraded DNA or inadequate or faulty PCR amplification, as all DNA samples which yielded initial negative results were successfully amplified with a β- actin-specific primer set. Figure 2 panel a illustrates the results of agarose gel electrophoresis of the 233 bp KS330 233 PCR amplification products. The 233 bp PCR product (denoted by arrow) is identified in the lanes representing MM BMSC DNA (lanes 1, 3, 5, and 15) , but not in the lanes of MM BMMC DNA (lanes 2, 4, and 6) or NHL BMSC DNA (lane 7) and "normal" (lanes 8-13) patients. The positive control PCR product from the PEL cell line KS-1 and the negative control of placental DNA are found in lane 16 and lane 14, respectively. Figure 2 panel b illustrates the Southern transfer of the results of the agarose gel electrophoresis shown in Figure 2 panel a, above. The immobilized nucleic acids were hybridized with a 32 P-end-labeled 30 nt. control oligonucieotide complementary to an internal region of the KS330 233 viral sequence [See Figure 1 SEQ ID NO. 3a] . As expected, those DNA samples which had previously given negative results in the PCR amplification did not hybridize with the oligonucieotide probe. The KS330 233 PCR amplification products obtained from the BMSC DNA of 2 MM patients was cloned into the Bluescript M13 vector system (Stratagene) and sequenced. Sequencing results demonstrated a 2 nucleotide difference in the 233 bp KS330 233 amplification product of one MM patient and a 4 nucleotide difference in the amplification product of other patient with respect to the sequence reported by Chang, Y., et al., supra , illustrated in Figure 3 [SEQ ID No. 6] . Therefore, in all probability, the viral sequences detected in the MM BMSC DNA are identical to the those originally shown to be associated with Kaposi's sarcoma-associated herpesvirus-like virus (i.e. , KSHV/HHV-8) . EXAMPLE 5 IN SITU HYBRIDIZATION AND IMMUNOHISTOCHEMICAL STAINING OF BMSCs Following trypsinization to release the adherent cells from the walls of the culture vessel, the BMSCs were collected by centrifugation and fixed in formalin. The fixed cell pellets were embedded in parrafin, serially- sectioned using a microtome, and the individual sections placed on glass microscope slides. The paraffin section were deparaf-finized and immersed in 3% hydrogen peroxide to quench endogenous peroxidase activity. Following proteinase K digestion for 30 minutes at 37°C, the slides were sequentially incubated with 10% paraformaldehyde solution for 5 minutes at room temperature and glycine solution for 5 minutes at 37°C The slides were then dehydrated and air-dried, and cover slips were placed on each slide. The viral DNA was denatured by heating for 4 minutes at 95°C Each slide was then incubated for 18 hours at 37°C with a biotinylated probe diluted 1:100 to 1:300 in a hybridization solution containing 50% formamide, 2X SSC, Denhardt ' s solution, dextrose sulfate, and denatured salmon sperm DNA. The probe was the identical oligonucieotide utilized in for the Southern blot hybridization, consisting of a 30 nt . oligomer internal to the KS330 233 sequence in the "sense" orientation [SEQ ID No. 3a] . However, biotinylated thymidine was used as the label, rather than end-labeling with [D- 32 P] deoxycytidine triphosphate. The sequence of the probe was as follows and T denotes biotinylated thymidine: S'-TATGTTACGCCAAGCTTGGTACCGAGCTCT-S' [SEQ ID No. 3b, Sense] Following hybridization, the slides were washed in Tris-buffered saline containing 0.02% SDS. Subsequently, the slides were incubated with a monoclonal mouse anti- biotin antibody (Dako Corporation) , followed by horseradish peroxidase-conjugated rabbit anti-mouse and goat anti-rabbit immunoglobulins (Dako Corporation) . The resulting in situ hybridization was visualized by means of a diaminobenzidene reaction. Additionally, immunohistochemistry staining was performed to detect the endothelial cell-surface marker CD31 on the BMSCs using an anti-CD31 monoclonal antibody (Dako Corporation) and standard immunoperoxidase methods as described by Ho, J. , et al., 2 Applied Immunohistochem . 282-91 (1994). In si tu hybridization, utilizing the biotinylated 30 nt . oligonucieotide internal KSHV sequence probe [SEQ ID No. 3b], and immunohistochemical staining (hematoxylin counterstain) were performed on MM BMSCs. The results are illustrated in Figure 6 panels a-d. Figure 6 panel a illustrates the results of in si tu hybridization of the PEL cell line, KS-1, utilized as a positive control. The results indicate both KSHV-specific nuclear and cytoplasmic staining. In addition, the chromosomes in mitotic cells are stained (denoted by arrowhead) . The magnification utilized was 400x. Figure 6 panel b illustrates the results of in situ hybridization of the acute myelogenous leukemia cell line HL60. The results indicate that this cell line is negative for KSHV-specific sequences. The magnification utilized was 400x. Figure 6 panel c illustrates the results of in si tu hybridization of BMSCs from a MM patient. Similar to results obtained for the KS-1 cell line, the MM BMSCs demonstrated KSHV-specific staining in both the nuclear and cytoplasmic regions. It should be noted, however, that the MM BMSCs have lost their typical fibroblast morphology following trypsinization. The magnification utilized was 400x. Figure 6 panel d illustrates the results of immunohistochemical staining of BMSCs from a MM patient (same patient as in panel c) for the endothelial cell- surface marker CD31. The results indicate that the MM BMSCs are negative for the CD31 marker antigen. The magnification utilized was 400x. EXAMPLE 6 AMPLIFICATION OF BMMC AND BMSC RNA USING RT-PCR Total cellular RNA from the BMMCs/BMSCs was isolated utilizing RNAZOL ® (TelTest, Inc.) as per the manufacture's instructions. First strand synthesis was performed utilizing 100 Units Moloney Murine Leukemia Virus Reverse Transcriptase (MMLV-RT, BRL Laboratories) at 42°C for 1 hour with 3μg of total cellular RNA. A primer set consisting of 24 bp oligomers having the sequences: 5'-TCACGTCGCTCTTTACTTATCGTG-3' [SEQ ID No. 4] 5'-CGCCCTTCAGTGAGACTTCGTAAC-3' [SEQ ID No. 5] were utilized in the RT-PCR amplification reactions at a concentration of 5 pmol. The primers were initially established from the KSHV interleukin-6 (vIL-6) homolog sequences. See Moore, P.S., & Chang, Y., Detection of Herpesvirus-Like Sequences in Kaposi's Sarcoma Patients With and Without HIV Infection, 332 New Engl . J. Med. 1181-5 (1995); Neipel, F., et al., Human Herpesvirus 8 Encodes a Homolog of Interleukin-6, 71 J. Virol . 839-42 (1997), whose disclosures are incorporated herein by reference. To the reaction mixture was also added 2.5 Units of Tag polymerase (Perkin Elmer) ; 200Dm of each deoxynucleotide triphosphate; lOμl of 5X Reaction Buffer C (Invitrogen; containing: 1.5 mM magnesium chloride, 50 mM potassium chloride, 10 mM Tris-HCl (pH 9.0), and 0.1% Triton X-100) ; and PCR water (Invitrogen) to a final total volume of 50μl. The typical PCR reaction conditions consisted of, but were not limited to, 60 cycles at 58°C for 1 minute, 72°C for 1.5 minute, 94°C for 1 minute with a 5 minute initial denaturation at 95°C and a final 5 minute elongation step performed in a programmable thermo-cycler (MJ Research) . lOμl of the PCR product was electrophoresed on a 1% agarose gel, stained with ethidium bromide, and photographed. The expected PCR product was 695 bp in length. In order to establish a putative association between the presence of KSHV in the BMSCs of patients diagnosed with MM and the paracrine stimulation the myeloma cell growth by KSHV-derived interleukin-6 (vIL-6) secretion by the BMSCs, the detection of vIL-6 mRNA transcripts in MM BMSCs was attempted. The nucleotide [SEQ ID No. 7] and inferred amino acid [SEQ ID No. 8] sequences of vIL-6 are shown in Figure 5 panels a and b, respectively. Reverse Transcription PCR (RT-PCR) was performed utilizing a vIL-6-specific primer set [see Figure 1, SEQ ID No. 4 and 5] on BMSC total cellular RNA isolated from three MM and two "normal" patients. As illustrated in Figure 4, the presence of appropriately-sized (695 bp) vIL-6 transcripts were demonstrated in 3 of 3 MM BMSCs (lanes 1-3) , whereas 0 of 2 "normal" BMSC samples exhibited the transcript (lane 4 and 5) . Again, the specificity and selectivity of the RT-PCR amplification reaction was established by successful amplification of the latter, vIL-6-negative BMSC samples (lane 4 and 5) utilizing a μ-actin-specific primer set. The results of this amplification reaction yielded the appropriately- sized amplification product (650 bp) and are illustrated in lanes 6 and 7. Lane M denotes a 123 bp molecular weight ladder utilized as an RNA transcript size marker. EXAMPLE 7 AMPLIFICATION AND DETECTION OF KSHV-SPECIFIC SEQUENCES IN BMSCS OF MGUS PATIENTS Amplification was also performed utilizing genomic DNA from the BMSCs of five patients diagnosed with monoclonal gammopathy of undetermined significance (MGUS) . PCR amplifi-cation was performed of the genomic DNA samples in order to detect the KS330 233 sequence using a viral sequence-specific primer set [see Figure 1, SEQ ID NO. 1 and No. 2] . The PCR amplification reaction conditions were identical to those utilized for the PCR amplification of the genomic DNA isolated from BMSCs and BMMCs in MM patients. PCR amplification was performed on the genomic DNA samples in order to detect the KS330 233 sequence using a viral sequence-specific primer set [see Figure 1 SEQ ID No. 1 and No. 2] . The PCR amplification reaction conditions were identical to those utilized for the PCR amplification of the genomic DNA isolated from BMSCs and BMMCs in MM patients. The amplification results demonstrated the presence of the KS330 233 amplified product in two of the five MGUS patients . EXAMPLE 8 DENDRITIC CELL ENRICHMENT FROM PERIPHERAL BLOOD MONONUCLEAR CELLS AND PCR DETECTION OF KSHV Mononuclear cells were used to enrich for a population of cells that express CD68 (a macrophage marker) and CD83 (a dendritic cell marker) . The mononuclear cells were placed into PBS (Sigma, St. Louis, MO) containing 1% FBS and 0.2% sodium citrate (PBS-FBS medium) . Mononuclear cells were incubated in PBS-FBS medium with 10% Gammagard (Baxter Healthcare Corporation, Chicago, IL) at room temperature for 15 minutes. Anti- CD68 and -83 antibodies (Dako, Carpenteria, CA and Coulter, Miami, FL, respectively) at a concentration of 25μg/ml were added and incubated at 4°C for 30 minutes. The cells were washed twice with PBS-FBS to remove unbound antibody and incubated with Dynal immunoglobulin coated beads (Dynal, Inc., Oslo, Norway) at a ratio of 1 bead/100 cells at 4°C for 30 minutes with agitation. The cells were washed twice with PBS-FBS to remove unbound beads and centrifuged at 600 x g for 10 minutes. The cells were placed in a 15 ml tube and then onto an electromagnet (Dynal, Inc.) for 2 minutes at room temperature to bind cells to the magnet. Unbound cells were removed by gentle aspiration, released from the separator and resuspended in PBS-FBS medium. DNA was extracted and quantified as outlined above. PCR was performed with 100 ng (~ 15,000 cells worth) of genomic DNA extracted from peripheral blood mononuclear and dendritic cell enriched populations. As described above, a total of 45 cycles of PCR amplification was performed on all samples to detect the KS330 233 fragment of KSHV. PCR for β-actin was also performed on all DNA samples to evaluate their viability. Samples were processed in a blinded fashion. The positive control DNA was obtained from a pleural effusion lymphoma cell line, KS-I (gift from J.W. Said) , which is known to harbor KSHV. Said JW, et al . , Kaposi's Sarcoma Associated Herpesvirus (KSHV or HHV8) in Primary Effusion Lymphoma; Ultrastructu- ral Demonstration of Herpesvirus in Lymphoma Cells, 87 Blood 4937-4943 (1996) . The negative control was placental DNA (Stratagene, La Jolla, CA) . To eliminate the possibility of any bias in our results, the PCR assay was performed in a blinded fashion, and all samples were processed in a similar fashion. We obtained peripheral blood on 36 myeloma patients, 15 MGUS patients, 6 patients with other malignancies, and 11 normal individuals. DNA was extracted from unenriched peripheral blood mononuclear cells on a number of the myeloma patients. Because the unenriched mononuclear cell samples were negative by PCR for the KS330 233 fragment, we enriched the mononuclear cells for cells expressing CD68 and CD83 and performed PCR for KS330 233 on this enriched population. The PCR results demonstrate that the KS330 233 fragment was amplified from the DNA from the CD68/83 enriched population from 29 of 36 myeloma patients, 0 of 6 MGUS patients, and 1 of 11 of the normal volunteers (tables 1 and 2) . Five of six of the untreated myeloma patients were positive for the virus, 7 of 10 of the myeloma patients responding to conventional or high dose chemotherapy were positive; 15 of 16 of the myeloma patients relapsing after conventional or high dose chemotherapy were positive; 2 of 4 of the remaining myeloma patients, who had recently initiated therapy and were not yet evaluable for response or were receiving supportive care only, were positive for the virus. Table 1 PCR Results: MGUS and Multiple Myeloma (MM) PCR Results Patient Diagnosi Clinical Status Unenriched CD68/83 s Enriched El MGUS stable M spike Neg Pos E2 MGUS Neg Neg E3 MGUS nd Neg E4 MGUS nd Neg E5 MGUS nd Pos E6 MGUS nd Neg E7 MGUS nd Pos E8 MGUS nd Pos E9 MGUS nd Neg E10 MGUS nd Neg Ell MGUS Neg Neg E12 MGUS nd Neg E13 MGUS nd Neg E14 MGUS nd Neg E15 MGUS nd Neg 4/15 Relapsing after chemotherapy E16 MM relapsing after nd Pos conventional chemotherapy E17 MM relapsing after nd Pos conventional chemotherapy E18 MM relapsing after nd Pos conventional chemotherapy E19 MM relapsing after nd Pos conventional chemotherapy Table 1 PCR Results: MGUS and Multiple Myeloma (MM) PCR Results Patient Diagnosi Clinical Status Unenriched CD68/83 Enriched E20 MM relapsing after Neg Pos conventional chemotherapy E21 MM relapsing after Neg Pos conventional chemotherapy E22 MM relapsing after Neg Pos conventional chemotherapy E23 MM relapsing after Neg Pos conventional chemotherapy E24 MM relapsing after nd Pos conventional chemotherapy E25 MM relapsing after nd Neg conventional chemotherapy E26 MM relapsing after Neg Pos conventional chemotherapy E27 MM relapsing after nd Pos conventional chemotherapy E28 MM relapsing after nd Pos conventional chemotherapy E29 MM relapsing s/p autologous nd Pos PSCT E30 MM relapsing s/p autologous nd Pos PSCT E31 MM relapsing s/p autologous Neg Pos PSCT 15/16 Responding to treatment E32 MM responding to conventional nd Neg chemotherapy E33 MM responding to conventional Neg Pos Table 1 PCR Results: MGUS and Multiple Myeloma (MM) PCR Results Patient Diagnosi Clinical Status Unenriched CD68/83 Enriched chemotherapy E34 MM s/p allogeneic BMT, in Neg Pos remission E35 MM s/p autologous PSCT, in nd Neg remission E36 MM stable s/p autologous PSCT nd Pos E37 MM stable s/p autologous PSCT Neg Pos E38 *αM stable s/p autologous PSCT nd Pos E39 MM stable s/p autologous PSCT nd Pos E40 MM stable s/p autologous PSCT Neg Neg E41 MM stable s/p autologous PSCT nd Pos 7/10 Untreated E42 MM untreated nd Pos E43 MM untreated nd Pos E44 MM untreated Pos Pos E45 MM untreated Neg Neg E46 MM untreated nd Pos E47 MM untreated nd Pos 5/6 Unknown response to chemotherapy E48 MM chemotherapy initiated, nd Neg unknown response E49 MM indolent myeloma on Neg Pos bisphosphonate E50 MM s/p cycle 1 of conventional nd Pos Table 1 PCR Results: MGUS and Multiple Myeloma (MM) PCR Results Patient Diagnosi Clinical Status Unenriched CD68/83 Enriched chemotherapy E51 MM stable on bisphosphonate Neg Neg 2/4 nd=not done. Neg=negative. PSCT=perihperal stem Total MM 29/36 cell transplanation. Pos=positive. BMT=bone marrow transplantation. s/p=status post. Table 2 PCR Results: Control Subjects CD68/83 Patent Diagnosis ιl£XUlβU Enriched Cl Pancreatic Ca. nd Neg C2 Prostate Ca. Nd Neg C3 CNS glioma Neg Neg C4 Melanoma nd Neg C5 Non-Hodgkin's ymphona Neg Neg C6 Non-Hodgkin's Lymphona nd Neg 0/6 C7 Normal Neg Neg C8 Normal Neg Neg C9 Normal Neg Neg CIO Normal Neg Neg Cll Normal Neg Neg C12 Normal Pos Pos Table 2 PCR Results: Control Subjects PCR Results CD68/83 Patent Diagnosis Unenriched Enriched C13 Normal Neg Neg C14 Normal nd Neg C15 Normal nd Neg C16 Normal nd Neg C17 Normal nd Neg 1/11 nd=not done . Neg= ^negative . Pos=positive. Total 1/17 While embodiments and applications of the present invention have been described in some detail by way of illustration and example for purposes of clarity and understanding, it will be apparent to those individuals who are skilled within the relevant art that many additional modifications would be possible without departing from the inventive concepts contained herein. The invention, therefore, is not to be restricted in any manner except in the spirit of the appended claims.

Claims: Claims 1) A method for the treatment of a patient with multiple myeloma (MM) or monoclonal gammopathy of undetermined significance (MGUS) comprising administering to the patient a pharmaceutically-effective amount of an anti-viral agent effective against KSHV. 2) The method of claim 1 wherein administering said anti-viral agent prevents said MGUS patient from subsequently developing multiple myeloma or a related malignant disease. 3) A method for the treatment of a patient having KSHV- and/or IL-6-associated disease, wherein said KSHV- and/or IL-6-associated diseases do not include Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease, comprising administrating to the patient pharmaceutically-effective amount of an anti-viral agent effective against KSHV. 4) The method of claim 3 wherein said KSHV- and/or IL-6-associated diseases are selected from a group consisting of Alzheimer's disease, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosis, scleroderma, malignancies of the kidney, and malignancies of the head/ neck. 5) A method for the treatment of a patient with mul-tiple myeloma (MM) or monoclonal gammopathy of undetermined significance (MGUS) comprising administrating to the patient having KSHV-associated MM or MGUS an effective amount of an inhibitory nucleic acid, said inhibitory nucleic acid capable of inhibiting the replication and/or the expression of KSHV. 6) The method of claim 5 wherein said inhibitory nucleic acid is selected from a group consisting of DNA, RNA, PNA, or fragments, derivatives, or conjugates thereof. 7) The method of claim 5 wherein said inhibitory nucleic acid is conjugated with an anti-viral agent. 8) The method of claim 5 wherein said inhibitory nucleic acid is conjugated with a chemotherapeutic agent. 9) The method of claim 5 wherein the inhibitory nucleic acid is administered in an amount effective to prevent said MGUS patient from subsequently developing multiple myeloma or a related malignant disease. 10) A method for the treatment of a patient having a KSHV- and/or IL-6-associated disease, wherein said KSHV- and/or IL-6-associated diseases do not include Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease, by administering to the patient an effective amount of an inhibitory nucleic acid capable of inhibiting or blocking the replication and/or expression of KSHV. 11) The method of claim 10 wherein said KSHV- and/or IL-6-associated diseases are selected from a group consisting of Alzheimer's disease, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosis, scleroderma, malignancies of the kidney, and malignancies of the head/neck. 12) The method of claim 10 wherein said inhibitory nucleic acid is selected from a group consisting of DNA, RNA, PNA, or fragments, derivatives, or conjugates thereof. 13) The method of claim 10 wherein said inhibitory nucleic acid is conjugated with an anti-viral agent. 14) The method of claim 10 wherein said inhibitory nucleic acid is conjugated with an chemotherapeutic agent. 15) A method of treatment of a patient with multiple myeloma (MM) or monoclonal gammopathy of undetermined significance (MGUS) comprising administrating to the patient an effective amount of an antibody, wherein said antibody is capable of inhibiting or blocking the replication or expression of KSHV. 16) The method of claim 15 wherein said antibody is selected from the group consisting of polyclonal antibodies, monoclonal antibodies, and a fragment, derivative, or conjugate thereof. 17) The method of claim 16 wherein said antibody is conjugated with an anti-viral agent. 18) The method of claim 16 wherein said antibody is conjugated with a chemotherapeutic agent. 19) The method of claim 15 wherein administering said antibody slows down the progression of MGUS in said patient to multiple myeloma (MM) or a related malignant disease. 20) The method of claim 19 wherein administering said antibody prevents said MGUS patient from subsequently developing multiple myeloma (MM) or a related malignant disease. 21) A method for the treatment of a patient having a KSHV- and/or IL-6-associated disease, wherein said KSHV- and/or IL-6-associated diseases do not include Kaposi's sarcoma (KS) , primary effusion lymphoma (PEL) , and multicentric Castleman's disease (MCD), comprising administrating to the patient an effective amount of an antibody, wherein said antibody is capable of inhibiting or blocking the replication or expression of KSHV. 22) The method of claim 21 wherein said KSHV- and/or IL-6-associated diseases are selected from a group consisting of Alzheimer's disease, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosis, scleroderma, malignancies of the kidney, and malignancies of the head/neck. 23) The method of claim 21 wherein said said antibody is selected from the group consisting of polyclonal antibodies, monoclonal antibodies, and a fragment, derivative, or conjugate thereof. 24) The method of claim 23 wherein said antibody is conjugated with an anti-viral agent. 25) The method of claim 23 wherein said antibody is conjugated with a chemotherapeutic agent. 26) A method of vaccinating a subject against multiple myeloma (MM) or monoclonal gammopathy of undetermined significance (MGUS) , comprising administering to the subject an effective amount of a KSHV-specific immunogen. 27) The method of claim 26 wherein said KSHV- specific immunogen is selected from a group comprised of whole virus, peptide, polypeptide, nucleic acid, protein nucleic acid, or fragments or derivatives thereof. 28) The method of claim 26 wherein administering said KSHV-specific immunogen slows down the progression of MGUS in said patient to multiple myeloma (MM) or a related malignant disease. 29) The method of claim 28 wherein administering said KSHV-specific immunogen prevents said MGUS subject from subsequently developing multiple myeloma (MM) or a related malignant disease. 30) A method of vaccinating a subject against KSHV- and/or IL-6-associated disease, said KSHV- and/or IL-6- associated diseases do not include Kaposi's sarcoma (KS) , primary effusion lymphoma (PEL) , and multicentric Castleman's disease (MCD), comprising administering to the subject an effective amount of a KSHV-specific immunogen. 31) The method of claim 30 wherein said KSHV- and/or IL-6-associated diseases are selected from a group consisting of Alzheimer's disease, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosis, scleroderma, malignancies of the kidney, and malignancies of the head/neck. 32) The method of claim 30 wherein said KSHV- specific immunogen is selected from a group comprised of whole virus, peptide, polypeptide, nucleic acid, protein nucleic acid, or fragments or derivatives thereof. 33) A method for determining the clinical efficacy of therapy in patients diagnosed with multiple myeloma (MM) , monoclonal gammopathy of undetermined significance (MGUS) , or related disorders by detecting KSHV-specific nucleic acid or peptide sequences in biological samples derived from these patients, said method comprising the steps of: a) providing an initial biological sample and at least one subsequent biological sample at a time later than the initial sampling; b) determining the amount of KSHV-specific nucleic acid or peptide sequences in said biological samples, c) comparing the amounts of KSHV-specific nucleic acid or peptide sequences in sequences taken before and after administration of therapy, and d) detecting whether the amount of KSHV- specific nucleic acid or peptide sequences in said biological samples has decreased after administration of therapy. 34) The method of claim 33 wherein the initial sample is taken before the administration of therapy. 35) The method of claim 33 wherein at least one subsequent sample is taken during administration of therapy. 36) The method of claim 33 wherein said biological samples are selected from a group consisting of blood, blood components, secretions, cells, sub-cellular components, tissues, or organs from patients diagnosed with multiple myeloma (MM) or monoclonal gammopathy of undetermined significance (MGUS), or related disorders. 37) The method of claim 33 wherein the biological sample is taken from the whole bone marrow aspirates, non- malignant bone marrow stromal cells, peripheral blood, or circulating dendritic cells from peripheral blood. 38) A method for monitoring the efficacy of therapy in patients with KSHV- and/or IL-6-associated disease, wherein said KSHV- and/or IL-6-associated diseases do not include Kaposi's sarcoma (KS) , primary effusion lymphoma (PEL), and multicentric Castleman's disease (MCD), by detecting KSHV-specific nucleic acid or peptide sequences in biological samples derived from these patients, said method comprising the steps of: a) providing an initial biological sample and at least one subsequent biological sample at a time later than the initial sampling; b) determining the amount of KSHV-specific nucleic acid or peptide sequences in said biological samples, c) comparing the amounts of KSHV-specific nucleic acid or peptide sequences in sequences taken before and after administration of therapy, and d) detecting whether the amount of KSHV- specific nucleic acid or peptide sequences in said biological samples has decreased after administration of therapy. 39) The method of claim 38 wherein the initial sample is taken before the administration of therapy. 40) The method of claim 38 wherein at least one subsequent sample is taken during administration of therapy. 41) The method of claim 38 wherein said biological samples are selected from a group consisting of blood, blood components, secretions, cells, sub-cellular components, tissues, or organs from patients diagnosed with multiple myeloma (MM) or monoclonal gammopathy of undetermined significance (MGUS), or related disorders. 42) The method of claim 38 wherein the biological sample is taken from the whole bone marrow aspirates, non- malignant bone marrow stromal cells, peripheral blood, or circulating dendritic cells from peripheral blood. 43) The method of claim 38 wherein said KSHV- and/or IL-6-associated diseases are selected from a group consisting of Alzheimer's disease, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosis, scleroderma, malignancies of the kidney, and malignancies of the head/neck. 44) A method for the detection of KSHV in a patient with multiple myeloma (MM) or monoclonal gammopathy of undetermined significance (MGUS) comprising the steps of a) acquiring a sample of i) non-malignant bone marrow cells or ii) circulating preipheral blood dendritic cells from said patient; b) amplifying KSHV sequences with KSHV- specific primers; and c) detecting the amplified KSHV sequences.

Inventors: BERENSON JAMES R, RETTIG MATTHEW B, VESCIO ROBERT A, BERENSON, JAMES, R., RETTIG, MATTHEW, B., VESCIO, ROBERT, A.
Applicants: BERENSON JAMES R, RETTIG MATTHEW B, VESCIO ROBERT A, BERENSON, JAMES, R., RETTIG, MATTHEW, B., VESCIO, ROBERT, A.
Application year: 1998
Main classification: A61K31
IPC codes: A61K38, A61K39, C07K14