DNA sequences derived from the genome of the papillomavirus HPV39, their use in in vitro diagnosis and for the production of an immunogenic composition

Specific DNA sequences derived from the genome of papillomavirus HPV 39 are provided. Also provided are hybridization probes, and methods for diagnosing genital neoplasias and for detecting infection by HPV 39.

FIELD OF THE INVENTION 
The invention relates to specific DNA sequences derived from the genome of 
the papillomavirus HPV39, including the sequence corresponding to its 
entire genome as well as recombinant DNAs, in particular vectors 
containing these DNA sequences. The invention also relates to the cell 
cultures transformed with the said recombinant DNAs under conditions 
making it possible for them to express the corresponding sequences derived 
from the HPV39 genome in the form of the corresponding proteins. Finally, 
the invention relates to the purified proteins obtained from these cell 
cultures. Finally, the invention relates to the production of the 
immunogenic compositions containing such proteins or protein fragments. 
BACKGROUND OF THE INVENTION 
The invention is based on the discovery of specific sequences present in 
HPV39, sequences which constitute its originality and which make possible 
particularly discriminating detection of papillomaviruses of the HPV39 
type. These sequences or fragments of these sequences can be used for 
constituting particularly sensitive hybridization probes, in particular, 
primers which make possible analyses by the so-called PCR method. Before 
proceeding further with the description of these sequences or sequence 
fragments, it is proposed to make a brief review of the state of the art 
and, then, to provide a detailed description of the genome of HPV39. 
Among the 60 if not more different types of human papillomaviruses, some 
are associated with neoplasias or with carcinomas of the genital apparatus 
(1). The DNA of HPV16 and HPV18 were detected in 50% and 20% of the 
biopsies of cervical, vulvar or penile cancer (2,3). The HPV 31, 33, 35, 
39 and 45 were encountered less frequently in such lesions (1,4). By using 
the DNA of HPV6 as a hybridization probe under conditions of low 
stringency, HPV39 was first cloned from biopsy samples of Bowenoid penile 
papules, which contain the viral DNA in its episomal form. On the other 
hand, the viral DNA was found to be integrated into the cellular genome of 
invasive carcinomas (5). In a recent study performed on 365 patients 
infected with HPV, the DNA of HPV39 was detected in 3.9% of the tissue 
samples. 
The biological study of HPV has been hindered by the absence of a tissue 
culture system for in vitro viral propagation. The analysis of the 
sequence of a certain number of papillomavirus genomes (2, 3, 6-14) has 
provided the basis for the understanding of their genetic organization and 
their regulation, for the expression of individual genes and the 
generation of antisera, and for the evaluation of the phylogenetic 
relationships among the very many types of HPV.

DESCRIPTION OF THE PREFERRED EMBODIMENTS 
The complete nucleotide sequence of the HPV39 genome has been determined. 
HPV39 DNA isolated from the original clone (5) was subcloned into pUC18 in 
three fragments of similar size by using the unique EcoRI site and the two 
BamHI sites. Clones suitable for the sequencing of a DNA strand were 
generated by creating detection series with the aid of the exonuclease III 
according to the procedure of Henikoff (15). The second strand was 
sequenced by using synthetic oligonucleotides complementary to the first 
strand as primers. The sequencing of the double-stranded plasmid was 
performed by using the dideoxy chain termination method of Sanger et at. 
(16, 17). 
The DNA of HPV39 comprises 7833 bp (FIG. 1) and exhibits a G/C content of 
40%. The restriction map derived from the sequence was confirmed by 
digestion of the DNA. It is in agreement with the restriction map 
published by Beaudenon et at. (5), with the exception of an additional 
HindII site, an additional PvuII and four additional AvaII sites. A AvaII 
site (at position 3592) is resistant to cleavage after cloning in E.coli 
on account of an overlapping with the recognition sequence for the dcm 
methylase of E. coli. 
HPV39 exhibits a set of open reading frames (ORFs) conserved in all of the 
HPVs sequenced hitherto (FIG. 2a, Table 1). The ORFs coding for the 
supposed early proteins and for the components of the capsid are localized 
on the same DNA strand; they are separated by a non-coding region (NCR) of 
782 base pairs (bp). The genomic characteristics shared by HPV39 with 
other genital papillomaviruses are shown by the overlappings between the 
ORFs E1 and E2, L2 and L1, the inclusion of E4 within E2, the localization 
of E7 immediately upstream from E1 (3) and the absence of the initiation 
codon ATG in E4, as was previously described for HPV16, 31 and 33 (2, 4, 
12). 
The DNA strands complementary to all of the genomes sequenced hitherto do 
not contain ORFs exceeding a size of 0.6 to 0.8 kb. The functional meaning 
of such ORFS was disproved by the absence of any detectable regulatory 
sequence. Furthermore, it has not been possible to demonstrate that they 
were transcribed in cells transformed by HPV or infected by BPV (7, 9, 18, 
19). One large ORF of 1.3 kb has now been found in this DNA strand of 
HPV39 (nucleotides 2050-776), which includes a ATG codon and a potential 
acceptor splicing site (GCTGCTACAGG (SEQ ID NO: 1), nucleotides 1871-1861) 
close to the 5' end (FIG. 2b). Further upstream on the same DNA strand, a 
minor ORF (nucleotides 4204-3875) is preceded by a TATA sequence at a 
distance of 23 bp (nucleotide 4227) and a binding site for the nuclear 
factor I (nucleotide 4271) (20, 21). At the 3' end of the ORF of 1.3 kb, a 
AATAAA polyadenylation signal (nucleotide 411) might be used for the 
maturation of a primary transcription product (22). Further experiments 
ought to make it possible to know whether this ORF is transcribed in vivo. 
The non-coding region of HPV39 is divided into three segments by three 
complete versions and two degenerate versions of the palindrome 
ACCGNNNNCGGT (SEQ ID NO: 2) specific for the papillomaviruses (nucleotides 
43, 59, 7456, 7625, 7798), an E2-dependent enhancer motif (23, 24). These 
segments correspond to sections of similar size in the genomes of HPV16, 
18 and 33 (3). There are two TATA box sequences in the non-coding region, 
one of them being localized upstream from the ORF E6. This latter probably 
constitutes a part of the E6 promoter and other early genes, in 
association with a conserved promoter AAAGGGAGTA (SEQ ID NO: 3) placed 
upstream from the tandem-repeated sequences of the palindrome of 12 bp 
(25-27). The presumed polyadenylation site for the products of late vital 
transcription is localized at a site situated at about 100 base pairs 
downstream from the stop codon L1. Another AATAAA element situated 
downstream from the E5 ORF might serve as polyadenylation signal for the 
products of early transcription (18). 
The long control regions of the previously sequenced genital HPVs contain 
binding sites for many transcription factors and were presented as 
functioning as specific enhancers of the cellular type for HPV6, 11, 16 
and 18 (28-30). The regulatory region of HPV39 contains four possible 
binding sites for the nuclear factor I (NFI) (21, 31), two for the 
activation protein 1 (AP1) (21, 32), a binding motif for "the factor 
associated with the papillomavirus enhancer" recently described 
(papillomavirus enhancer associated factor: PVF) (31), and one "core 
enhancer sequence" conserved in SV40 and in other viruses (33) (FIG. 3). A 
potential element involved in the glucocorticoid response (glucoprotein 
response element: GRE) resembles those which are found in the NCRs of 
related HPV types (27). An additional highly conserved GRE element found 
in the ORF (nucleotide 6367) has no equivalent in other types of HPV (FIG. 
4). It overlaps with an AP2 binding site that it is also found in the 
enhancers of SV40 and BPV (34). That indicates the presence of a 
regulatory function for the region situated upstream from the NCR. A 
cooperative effect of NFI and AP1, as well as of NP] with the 
glucocorticoid receptor respectively has been described for the enhancer 
of HPV16 (30). The interaction of many factors with potential binding 
sites in the NCR and in L1 of HPV39 has still to be elucidated. Donor 
(nucleotide 233) and acceptor (nucleotide 408) splicing sites are 
localised downstream from the NCR. They were demonstrated to be important 
for the generation of the E7 mRNA in the oncogenic types of HPV (4, 35). 
Comparisons of individual ORF sequences indicate that HPV39 has the highest 
degree of homology with HPV18. It is more distantly related to other 
genital papillomaviruses, and less still with a member of the cutaneous 
types of HPVs, HPV8 (Table 2). Thus HPV39 belongs to a subgroup of genital 
HPVs exhibiting a considerable oncogenic potential which includes HPV18, 
HPV45(1) and a novel type showing a strong homology with HPV39 recently 
cloned from a cell line of the carcinoma ME180 distinct from the 
HPV16/31/33 group. 
The ORFs E6 and E7 are usually transcribed in the cell lines of the 
cervical cancer and carcinoma (36), and the products of their genes are 
implicated in the immortalization and transformation of primary epithelial 
cells and fibroblasts (37). Four Cys---Cys (SEQ ID NO: 4) motifs in the E6 
protein of all of the sequenced papillomaviruses, which might be 
implicated in the binding of DNA as a result of the formation of 
structures of the "zinc finger" type (38), are also present in HPV39. On 
the other hand, only the first of the two well-conserved Cys---Cys (SEQ ID 
NO: 4) elements can be found in the E7 protein. The second element has a 
cysteine substituted by a tyrosine. Since the mutational analysis of the 
ORF E7 of HPV16 has made it possible to demonstrate that one "zinc finger" 
is sufficient for transformational capacity (39), the E7 protein of HPV39 
probably remains functional. Furthermore, the E7 protein of HPV39 contains 
a "cell division protein (cd)" motif which is common to many products of 
genes implicated in transformation, such as the T antigen of SV40, E1A of 
adenovirus, the myc protein and the E7 proteins of the malignant genital 
HPVs, but not of HPV6 or HPV11 (4): 
asp/asn-x-x-cys x-ser/thr/glu-x-(1-8)-asp/glu-asp/glu/ser/ thr-asp/glu (SEQ 
ID NO: 5) (the amino acids of E7 of HPV39 are underlined). The cd motifs 
of the large T antigen of SV40 and of the protein of the adenovirus seem 
to be responsible for the binding of the anti-oncogenic product of the 
retinoblastoma (40). The transformational activity of E7 may also be 
attributable to a protein-protein interaction via the cd sequence. 
The invention relates more particularly to the sequence corresponding to 
the large ORF of 1.3 kb extending from the nucleotide 2050 to the 
nucleotide 776 of FIG. 1 or to any fragment contained in this sequence or 
which may be derived from it, this fragment containing at least 15 
nucleotides. 
The invention also relates even more particularly to the sequence 
corresponding to the minor ORF extending from nucleotide 4204 to 
nucleotide 3875 and even from nucleotide 4227 to nucleotide 3875 or 
sequences derived from these latter. 
Similarly the invention also relates to sequences of at least 15 
nucleotides derived from the entire sequence of HPV39 and comprising at 
least 15 nucleotides and containing the highly conserved GRE element at 
the nucleotide 6367 and more particularly emphasized in FIG. 4. Finally, 
the invention relates more specifically to the 3 nucleotide sequences 
identified below: 
Consensus: GGTACANNNTGTTCT (SEQ ID NO: 6) 
HPV39 (NCR): TCTACATTTTATACT (SEQ ID NO: 7) 
HPV39 (L1): GGGACAGTATGTTCT (SEQ ID NO: 8) 
The invention also relates to all fragments, the sizes of which do not 
exceed those of the fragments previously defined, the former being 
characterized in that they hybridize with the latter under strict 
conditions (Tm -20.degree. C.), particularly when the following conditions 
are used: 
Hybridization is carried out at 42.degree. C. in a solution containing: 50 
mM of sodium phosphate buffer, pH=6.5; 5.times. SSC (1.times. SSC=0.15M 
NaCl, 0.015M Na citrate); 50% formamide; 200 ug/ml of yeast transfer RNA; 
0.02% of Denhart solution. 
Also forming part of the invention are the fragments belonging to the same 
types, in particular in that they exhibit percentages of cross 
hybridization higher than 50% with the fragments defined more specifically 
above. 
The use of one or other of the sequences mentioned above or nucleic acids 
containing them are particularly suitable for constituting the 
hybridization probe which makes possible the detection of a papillomavirus 
DNA related to HPV39 in a biological sample. 
Generally speaking, the invention thus also relates to any recombinant DNA 
containing the above-mentioned HPV-DNA or fragments of this HPV-DNA, in 
particular hybridization probes formed from these recombinant DNAs and 
specially adapted to the detection of an infection by HPV39 or by a 
variant or subtype of this papillomavirus. These probes may be either 
labelled themselves or modified at certain nucleotides, in particular for 
the purpose of coupling them directly or indirectly with a separate 
marker. It will be obvious that in such probes the parts foreign to the 
nucleotide sequence corresponding to the DNA of the papillomavirus are 
such that there is no risk of their hybridizing under stringent conditions 
with the other nucleic acids possibly contained in the sample tested for 
the possible presence of DNA of the corresponding papillomavirus or one of 
its variants. 
The procedure according to the invention for the in vitro diagnosis, in a 
biological sample to be tested usually obtained from a human patient, of 
an infection by a papillomavirus capable of leading to or having led to a 
genital neoplasia, in particular a cervical, vulvar or penile cancer, is 
hence characterized by placing a probe such as that defined above in 
contact with the nucleic acid of this sample, made accessible to the probe 
beforehand where necessary, preferably under stringent conditions of 
hybridization, and by detection of the hybrid formed between the vital DNA 
under investigation and possibly present in the sample and the said probe. 
Each of the probes according to the invention or the mixtures containing 
the above-mentioned probe can, in particular, be used as follows, it being 
naturally understood that the diagnostic tests described are not to be 
considered as limiting the conditions of use under which these probes or 
mixtures of probes may in fact be used. 
In the example considered, the purpose is to identify a HPV in a biopsy, in 
cells obtained/by scratching of lesions, or in biopsy sections fixed by 
means of the Carnoy mixture (ethanol, chloroform, acetic acid 6:3:1) and 
embedded in paraffin. The examination necessitates the prior extraction of 
the DNA from samples according to methods, the principle of which is known 
and involves the analysis of this DNA by molecular hybridization 
experiments carried out under stringent or less stringent conditions with 
the aid of radioactive probes (labelled with .sup.32 P or .sup.35 S) 
prepared from the HPV according to the invention or mixtures of DNAs or 
HPVs containing it. 
Several methods of hybridization may be used. It is possible, for example, 
to employ the dot method of hybridization. After denaturation of the DNA, 
this method comprises the deposition of aliquot amounts of DNA on 
membranes (nitrocellulose or "Genescreenplus"), the hybridization of each 
membrane under the usual conditions with a mixture of probes and the 
detection of the radioactive hybrids by exposure of the membranes to 
contact with a radiographic film. It is also possible to use the replica 
method of hybridization. This method comprises the electrophoretic 
separation of the DNA fragments obtained after treatment of the DNA with 
restriction enzymes in an agarose gel, the transfer of the fragments to 
membranes (nitrocellulose, "Genescreenplus") after alkaline denaturation 
and their hybridization under the usual conditions with the appropriate 
mixture of probes. The formation of radioactive hybrids is detected after 
exposure of the membranes to contact with a radiographic film. 
The radioactive probes are constituted either by DNAS of HPVs labelled by 
the method of "nick translation" or by RNAs prepared by transcription of 
vital DNAs inserted in a vector, for example of the SP6 type. The use of 
radioactive probes has the advantage of high sensitivity but this does not 
exclude the use of non-radioactive probes, for example biotinylated probes 
capable of being recognized by antibodies either labelled themselves or 
which are themselves recognized by antibodies bearing an enzymatic, 
fluorescent or other type of label. 
The invention also relates to competent cell cultures transformed with 
recombinant DNAs of the type indicated above, in particular those in which 
the nucleotide sequence corresponding to the DNA or the sequence of the 
DNA of HPV39 is placed under the control of transcription and regulatory 
elements for this nucleotide sequence in the said cell culture. 
Consequently, the invention also relates to the products of expression of 
these recombinant DNAs in the corresponding competent cell hosts and the 
corresponding antibodies capable of being produced against these 
expression products. 
Consequently, the invention relates to the polypeptides resulting in 
particular from the expression of the genes E1, E2, E4, E6, E7, L1, L2 of 
the HPV39-DNA, respectively. 
The procedure according to the invention for the production of these 
polypeptides consequently comprises the transformation of competent cell 
cultures with the recombinant DNAs containing the corresponding nucleotide 
sequences derived from HPV39, such that the nucleotide sequence 
corresponding to one of the said proteins can be expressed in this cell 
host, the recovery of these polypeptides from the products synthesized by 
the competent cell host and the purification (for example, by placing the 
expression products previously extracted from the cell cultures or from 
the medium in which the latter were grown in contact with antibodies 
previously formed against such peptides). 
The expression products of the L2 sequences of each of the genomes of the 
papillomaviruses according to the invention have however a quite special 
value in that they may themselves be used for the in vivo production of 
antibodies capable of recognizing the expression products of the L2 gene 
in biological samples infected by a papillomavirus of the HPV39 type or by 
a variant of the latter, and more particularly when the preparations of 
the type in question have been fixed. 
The invention also relates to hybrid polypeptides containing the 
above-mentioned polypeptides and derivatives respectively of HPV39, for 
example the L2 protein fused with other polypeptide sequences provided 
that the latter do not modify essentially the immunogenic properties of 
the L2 protein. The presence of these other polypeptide fragments may also 
result from the method used to produce these hybrid polypeptides, for 
example by means of genetic engineering. For example, these hybrid 
polypeptides contain a sequence derived from beta-galactosidase. Such 
products may be obtained in particular by transformation of E. coli with 
suitable vectors (phages or plasmids) modified by all or part of the 
lactose operon and containing, in addition, inserted downstream from the 
promoter of the lactose operon (or any other suitable promoter, for 
example of phage lambda), the nucleotide sequence derived from the L2 gene 
derived from HPV39. Recourse is advantageously had to plasmids or phages 
of this type comprising at least a part of the gene for the 
beta-galantosidase of the lactose operon. 
When they have been purified, the polypeptides according to the invention 
may also be used in purification procedures for the antibodies which 
correspond to them, in particular from the sera of animals which had been 
immunised by these polypeptides. In particular, these polypeptides may be 
bound to affinity column. The steps entailed in the purification of the 
antibodies then consist of passing the serum containing them through 
affinity columns beating the polypeptides mentioned above. The antibodies 
selectively bound to these columns can then be recovered by dissociation 
of the antigen-antibody complexes by means of a suitable buffer of 
sufficient ionic strength, for example an aqueous solution of a salt such 
as ammonium acetate. It is also possible to have recourse to acidified 
solutions. 
The invention also relates to a procedure for the production of antibodies 
against the said polypeptides, in particular against the expression 
products of the genes E6, E7 or preferably L2 of HPV39, this procedure 
comprising the immunization of a suitable live host with the said 
polypeptides and the recovery of the antibodies formed from a serum of the 
immunized host, in particular by placing these sera in contact with the 
corresponding polypeptides in the purified state and the recovery of these 
antibodies from the antigen-antibody complexes formed. 
In particular, the invention relates to the above-mentioned antibodies, 
purified beforehand, in combination with a suitable pharmaceutical 
vehicle. This composition is then capable of being used for the treatment 
of the infection concerned, provided that the latter has been clinically 
diagnosed as the result of an in vitro diagnostic assay on a histological 
or cytological specimen taken from a patient. This composition (in 
particular in the form of a serum) may be administered preferably by the 
parenteral route. This serum is then capable of causing a regression of 
the infections induced by papillomaviruses of the HPV39 type. 
These antibodies can be used more particularly in diagnostic assays of an 
infection due to HPV39 or to a related papillomavirus (or to a variant of 
this papillomavirus), provided that histological sections derived from 
infected persons also contain expression products of some of its 
structural genes, in particular L2. 
Hence the invention also relates to a procedure of in vitro diagnosis of 
genital neoplasias, in particular of cervical, vulvar or penile cancers, 
comprising the placing of histopathological sections taken from lesions 
induced in the persons concerned under conditions leading to the 
production of an antigen-antibody complex and the detection of this 
antigen-antibody complex. Advantageously, the detection is performed on 
preparations fixed beforehand under dissociating conditions, for example 
with the Carnoy solution or mixture already mentioned above (also 
described in the monograph by L. LISON, entitled "Histochimie et 
cytochimie animales"). 
The anti-L2 antibodies possibly bound can be recognized by other antibodies 
formed against the former, these latter antibodies bearing suitable, 
preferably non-radioactive, markers. These markers are, for example, 
enzymatic or fluorescent in nature. 
The antibodies thus selected, like the hybridization probes defined above 
to which they correspond, may consequently be used to diagnose in vitro 
the corresponding types of infections. 
Finally, the invention relates to the corresponding vaccinating 
compositions containing one or preferably several other L2 proteins, in 
combination with a pharmaceutically acceptable vehicle suited to the 
selected mode of administration, particularly by the parenteral route. 
These compositions can be used to protect the persons subjected to high 
risks of infection by HPV39 or by papillomaviruses of a corresponding 
type. 
TABLE 1 
______________________________________ 
OPEN READING FRAMES (ORF) 
THE STRAND SIMILAR TO THE mRNA OF THE HPV39 GENOME 
Nucleotide 
preceding 
ORF Molecular 
First First the stop size weight 
ORF nucleotide 
ATG codon (bp) (kD) 
______________________________________ 
E6 44 107 580 537 18.7 
E7 493 592 918 426 12.5 
E1 922 928 2868 1947 73.0 
E2 2780 2798 3907 1128 43.0 
E4 3393 -- 3674 282 -- 
E5 3958 3958 4173 216 9.0 
L2 4172 4250 5659 1488 49.9 
L1 5610 5643 7157 1548 56.0 
______________________________________ 
TABLE 2 
______________________________________ 
COMISON OF HPV PROTEINS WITH HPV39 
(PERCENTAGES OF IDENTICAL AMINO ACIDS) 
HPV18 HPV33 HPV16 HPV11 HPV8 
______________________________________ 
E5 68% 51% 48% 38% 26% 
E1 71% 55% 48% 51% 40% 
E2 53% 47% 49% 47% 33% 
L2 71% 53% 56% 50% 37% 
L1 77% 66% 65% 65% 54% 
______________________________________ 
a The sequence comparisons were made by having recourse to a computer 
programme based on an algorithm of Needleman and Wunsch (41). 
REFERENCES 
1. De Villiers, E. J. Virol. 63, 4898-4903(1989). 
2. Seedorf, K., Krammer, G., Durst, M., Suhai, S. and Rowekamp, W. G., 
Virology 145, 181-185 (1985). 
3. Cole, S. T. and Danos, O. J. Mol. Biol. 193, 599-608 (1987). 
4. Goldsborough, M. D., DiSilvestre, D., Temple, G. F. and Lorinez, A. T., 
Virology 171, 306-311 (1989). 
5. Beaudenon, S., Kremsdorf, D., Obalek, S., Jabionska, S., Pehau-Arnaudet 
G., Croissant, O. and Orth, G., Virology 161, 374-384 (1987). 
Danos, O., Katinka, M. and Yaniv, M., EMBO J. 1, 231-236 (1982). 
7. Chen. E., Howley, P. M., Levinson, A. D., Seeburg, P. H., Nature 299, 
529-534 (1982). 
8. Dartmann, K., Schwartz, E., Gissmann, L. and Zur Hausen, H., Virology 
151, 124-130 (1986). 
9. Fuchs, P. G., Ifiner, T., Weninger, J. and Pfister, H., J. Virol. 58, 
626-634 (1986). 
10. Giri, I., Danos, O. and Yaniv, M., Proc. Natl. Acad. Sci. USA 82, 
1580-1584 (1985). 
11. Groff, D. E. and Lancaster, W. D., J. Virol. 56, 85-91 (1985). 
12. Cole, S. T. and Streeck, R. E., J. Virol. 58, 991-995 (1986). 
13. Schwarz, E., Durst, M., Demankowski, C., Lattermann, O., Zech, R., 
Wolfsperger, E., Suhai, S. and Zur Hausen, H., EMBO J. 2, 2341-2348 
(1983). 
14. Zachow, K. R., Ostrow, R. S., Faras, A. J., Virology 158, 251-254 
(1987). 
15. Henikoff, S., Methods in Enzymology 155, 156-165 (1987). 
16. Sanger, F., Nicklen, S. and Coulson, A. R., Proc. Natl. Acad. Sci. USA 
74, 5463-5467 (1977). 
17. Zhang, H., Scholl, R., Browse, J. and Somerville, C., Nuel. Acids Res. 
16, 1220 (1988) 
18. Chow, L. T., Nassen, M., Wolinsky, S. M. and Broker, T. R., J. Virol. 
61, 2581-2588 (1987). 
19. Engel, L. W., Heilman, C. A. and Howley, P. M., J. Virol. 47, 516-528 
(1983). 
20. Benoist, C. and Chambon, P., Nature 290, 304-310 (1981). 
21. Wingender, E., Nucl. Acids Res. 16, 1879-1902 (1988). 
22. Proudfoot, N., Nature 298, 516-517 (1982). 
23. Spaiholz, B. A., Yang, Y. and Howley, P. M., Cell 42, 183-191 (1985). 
24. Hirochika, H., Broker, T. R. and Chow, L. T., J. Virol. 61, 2599-2606 
(1987). 
25. Gloss, B., Chong, T. and Bernard, H. -U., J. Virol. 63, 1142-1152 
(1989). 
26. Thierry, F., Heam, J. M., Dartmann, K. and Yaniv, M., J. Virol. 61, 
134-142 (1987). 
27. Chan, W., Klock, G. and Bernard, H. -U., J. Virol. 63, 3261-3269 
(1989). 
28. Chin, M. T., Broker, T. R. and Chow, L. T., J. Virol. 63, 2967-2976 
(1989). 
29. Cripe, T. P., Haugen, T. H., Turk, J. P., Tabatabai, F. Schmid, P. G., 
Durst, M., Gissmann, L., Roman, A. and Turek, L. P., EMBO J. 6, 3745-3753 
(1987). 
30. Chong, T., Chan, W. K. and Bernard, H. -U., Nucl. Acids. Res. 18, 
465-470 (1990). 
31. Gloss, B., Yeo-Gloss, M., Meisterernst, M., Rogge, L., Winnacker, E. L. 
and Bernard, H. -U., Nucl. Acids. Res. 17, 3519-3533 (1989). 
32. Angel, P., Imagawa, M., Chin, R., Stein, B., Imbra, R. J., Rahmsdorf, 
H. J., Jonat, C., Herrlich, P. and Karin, M., Cell 49, 729-738 (1987). 
33. Weiher, H., Konig, M. and Gruss, P., Science 219, 626-631 (1983). 
34. Imagawa, M., Chin, R. and Karin, M., Cell 51, 251-258 (1987). 
35. Smotkin, D., Prokoph, H. and Wettstein, F. O., J. Virol. 63, 1441-1447 
(1989). 
36. Smotkin, D. and Wettstein, F. O., Proc. Natl. Acad. Sci. USA 83, 
4680-4684 (1986). 
37. Munger, K., Phelps, W. C., Bubb, V., Howley, P. M. and Schlegel, R., J. 
Virol. 63, 4417-4421 (1989). 
38. Evans, R. M. and Hollenberg, S. M., Cell 52, 1-3 (1988). 
39. Edmonds, C. and Vousden, K. H., J. Virol. 63, 2650-2656 (1989). 
40. Figge, J. and Smith, T. F., Nature 334, 109 (1988). 
41. Needleman, S. B. and Wunsch, C. D., J. Mol. Biol. 48, 443-450 (1970). 
__________________________________________________________________________ 
SEQUENCE LISTING 
(1) GENERAL INFORMATION: 
(iii) NUMBER OF SEQUENCES: 11 
(2) INFORMATION FOR SEQ ID NO:1: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 11 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: single 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: DNA (genomic) 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:1: 
GCTGCTACAGG11 
(2) INFORMATION FOR SEQ ID NO:2: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 12 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: single 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: DNA (genomic) 
(ix) FEATURE: 
(A) NAME/KEY: misc_feature 
(B) LOCATION: 5..8 
(D) OTHER INFORMATION: /N="unknown" 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:2: 
ACCGNNNNCGGT12 
(2) INFORMATION FOR SEQ ID NO:3: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 10 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: single 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: DNA (genomic) 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:3: 
AAAGGGAGTA10 
(2) INFORMATION FOR SEQ ID NO:4: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 4 amino acids 
(B) TYPE: amino acid 
(C) STRANDEDNESS: single 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: DNA (genomic) 
(ix) FEATURE: 
(A) NAME/KEY: Peptide 
(B) LOCATION: 2..3 
(D) OTHER INFORMATION: /note="Xaa is unknown." 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:4: 
CysXaaXaaCys 
(2) INFORMATION FOR SEQ ID NO:5: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 18 amino acids 
(B) TYPE: amino acid 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: peptide 
(ix) FEATURE: 
(A) NAME/KEY: Peptide 
(B) LOCATION: one-of(3, 4, 6, 10) 
(D) OTHER INFORMATION: /note="Xaa is unknown." 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:5: 
AspAsnXaaXaaCysXaaSerThrGluXaaAspGluAspGluSerThr 
151015 
AspGlu 
(2) INFORMATION FOR SEQ ID NO:6: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 15 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: single 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: DNA (genomic) 
(ix) FEATURE: 
(A) NAME/KEY: misc_feature 
(B) LOCATION: 7..9 
(D) OTHER INFORMATION: /N="unknown" 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:6: 
GGTACANNNTGTTCT15 
(2) INFORMATION FOR SEQ ID NO:7: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 15 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: single 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: DNA (genomic) 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:7: 
TCTACATTTTATACT15 
(2) INFORMATION FOR SEQ ID NO:8: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 15 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: single 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: DNA (genomic) 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:8: 
GGGACAGTATGTTCT15 
(2) INFORMATION FOR SEQ ID NO:9: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 7833 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: single 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: DNA (genomic) 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:9: 
CTTATAACATTTTATAAGTATCTTGTTTAAAAAAAGGGAGTAACCGAAAACGGTCAGGAC60 
CGAAATCGGTGGATATAAAACGCAGTCACAGTTTCTGTCCATACCGATGGCGCGATTTCA120 
CAATCCTGCAGAACGGCCATACAAATTGCCAGACCTGTGCACAACGCTGGACACCACCTT180 
GCAGGACATTACAATAGCCTGTGTCTATTGCAGACGACCACTACAGCAAACCGAGGTATA240 
TGAATTTGCATTTAGTGATTTATATGTAGTATATAGGGACGGGGAACCACTAGCTGCATG300 
CCAATCATGTATAAAATTTTATGCTAAAATACGGGAGCTACGATATTACTCGGACTCGGT360 
GTATGCAACTACATTAGAAAATATAACTAATACAAAGTTATATAATTTATTAATAAGGTG420 
CATGTGTTGTCTGAAACCGCTGTGTCCAGCAGAAAAATTAAGACACCTAAATAGCAAACG480 
AAGATTTCATAAAATAGCAGGAAGCTATACAGGACAGTGTCGACGGTGCTGGACCACAAA540 
ACGGGAGGACCGCAGACTAACACGAAGAGAAACCCAAGTATAACATCAGATATGCGTGGA600 
CCAAAGCCCACCTTGCAGGAAATTGTATTAGATTTATGTCCTTACAATGAAATACAGCCG660 
GTTGACCTTGTATGTCACGAGCAATTAGGAGAGTCAGAGGATGAAATAGATGAACCCGAC720 
CATGCAGTTAATCACCAACATCAACTACTAGCCAGACGGGATGAACCACAGCGTCACACA780 
ATACAGTGTTCGTGTTGTAAGTGTAACAACACACTGCAGCTGGTAGTAGAAGCCTCACGG840 
GATACTCTGCGACAACTACAGCAGCTGTTTATGGACTCACTAGGATTTGTGTGTCCGTGG900 
TGTGCAACTGCAAACCAGTAACCTGCTATGGCCAATCGTGAAGGTACAGACGGGGATGGG960 
TCGGGATGTAACGGATGGTTTCTAGTACAGGCAATAGTAGATAAACAAACAGGCGACACA1020 
GTGTCGGAGGATGAGGATGAAAATGCAACAGATACAGGTTCAGACCTGGCAGACTTTATT1080 
GATGATTCCACAGATATTTGTGTACAGGCAGAGCGTGAGACAGCACAGGTACTTTTACAT1140 
ATGCAAGAGGCCCAAAGGGATGCACAAGCAGTGCGTGCCTTAAAACGAAAGTATACAGAC1200 
AGCAGTGGCGACACTAGACCGTATGGAAAAAAAGTAGGCAGGAATACCAGGGGAACACTA1260 
CAGGAAATTTCATTAAATGTAAGCAGTACGCAGGCAACACAAACGGTGTATTCCGTGCCA1320 
GACAGCGGATATGGCAATATGGAAGTGGAAACAGCTGAAGTGGAGGAGGTAACTGTAGCA1380 
ACTAATACAAATGGGGATGCTGAAGGGGAACATGGCGGCAGTGTACGGGAGGAGTGCAGT1440 
AGTGTGGATAGTGCTATAGATAGTGAAAACCAGGATCCCAAATCTCCAACTGCACAAATT1500 
AAATTATTGTTACAATCCAATAACAAAAAGGCTGCAATGCTAACACAATTTAAAGAAACA1560 
TATGGACTATCCTTTACTGACCTGGTACGTACGTTTAAAAGTGATAAAACAACATGTACA1620 
GACTGGGTGGCAGCCATATTTGGAGTACATCCAACTATTGCAGAAGGATTTAAAACATTA1680 
ATCAACAAATATGCCTTATATACACATATACAAAGCTTAGACACAAAACAAGGAGTACTA1740 
ATTTTAATGCTAATAAGATATACATGTGGAAAAAATAGGGTTACTGTAGGAAAGGGATTA1800 
AGTACATTGTTACATGTTCCAGAAAGTTGTATGCTTCTGGAGCCTCCTAAACTGCGCAGC1860 
CCTGTAGCAGCACTATATTGGTATCGCACAGGTATATCCAATATTAGTGTGGTAACAGGG1920 
GATACGCCAGAATGGATACAACGATTAACTGTTATACAACATGGAATAGATGATAGTGTA1980 
TTTGACCTATCGGACATGGTACAATGGGCATTTGACAATGAATATACTGATGAAAGTGAC2040 
ATAGCATTTAATTATGCAATGTTAGCAGATTGTAACAGTAATGCTGCAGCCTTTTTAAAA2100 
AGTAACTGCCAGGCAAAATATGTAAAAGATTGTGCAACAATGTGTAAACATTACAAGCGA2160 
GCACAAAAAAGGCAAATGTCCATGTCTCAATGGATAAAATTTAGGTGTAGTAAATGTGAT2220 
GAAGGCGGGGACTGGAGACCCATAGTACAATTCTTAAGATATCAAGGAATAGAATTTATA2280 
TCCTTTTTATGTGCATTAAAGGAATTTTTAAAGGGTACTCCCAAAAAAAACTGTATAGTT2340 
ATATATGGACCTGCGAATACAGGAAAGTCACATTTTTGTATGAGCCTTATGCATTTTTTA2400 
CAGGGCACAGTTATTTCATATGTAAACTCCACCAGCCACTTTTGGCTAGAACCACTTGCA2460 
GATGCAAAACTAGCAATGTTAGATGATGCAACCGGTACCTGCTGGTCATATTTCGATAAT2520 
TATATGAGAAATGCATTAGATGGGTATGCAATAAGTTTAGATAGGAAATATAAAAGTTTA2580 
CTACAAATGAAATGTCCACCATTATTAATAACCTCCAATACCAATCCTGTGGAAGACGAT2640 
AGGTGGCCATATTTACGTAGTAGGCTAACAGTGTTTAAATTTCCTAATGCATTTCCATTT2700 
GACCAAAACAGGAATCCAGTGTACACAATCAATGATAAAAACTGGAAATGTTTTTTTGAA2760 
AAGACTTGGTGCAGATTAGACTTGCAGCAGGACGAGGATGAAGGAGACAATGATGAAAAC2820 
ACTTTCACAACGTTTAAATGTGTTACAGGACAAAATACTAGAATACTATGAACAAGACAG2880 
TAAATCAATATATGATCAAATTAATTATTGGAAATGTGTGCGAATGGAAAATGCAATATT2940 
TTATGCAGCACGAGAACGTGGCATGCATACTATTGACCACCAGGTGGTGCCAACCATAAA3000 
CATTTCAAAATGTAAAGCATATCAAGCTATTGAACTGCAGATGGCACTAGAAAGTGTTGC3060 
ACAAACTGAATACAATACAGAGGAGTGGACATTAAAAGACACTAGTAATGAACTGTGGCA3120 
TACACAGCCAAAACAATGTTTTAAAAAACAAGGAACTACAGTGGAGGTGTGGTATGATGG3180 
GGACAAATGTAATGCTATGAACTATGTATTATGGGGTGCTATATATTATAAAAATAATAT3240 
AGACATATGGTGTAAAACAGAAGGGTGTGTGGACTATTGGGGTATATATTATATGAACGA3300 
GCACCTAAAAGTATACTATGAAGTGTTTATTCAAGATGCGGAAAGGTATGGGACTAGTGG3360 
CAAATGGGAAGTGCATTATAATGGCAACATAATTCATTGTCCTGACTCTATGTGCAGTAC3420 
CAGTGACGGATCGGTACCCACTACTGAACTTACTACCGAATTATCAAACACCACCGCGAC3480 
CCATTCCACCGCAACAACCCCATGCACCCAAAAAACAATCCCGCCGCCGTCTCGAAAGCG3540 
ACCTCGACAGTGTGCAGTCACAGAGCCCACTGAGCCCGACGGAGTGTCCCTGGACCATCT3600 
TAACAACCCACTCCACAGTAACAGTACAGGCCACAACACAAGACGGTACCTCAGTTGTGG3660 
TAACACTACGCCTATAATACATTTAAAAGGTGACAAAAATGGTTTAAAATGTTTAAGATA3720 
TAGACTACAAAAATATGACACATTGTTTGAAAATATTTCATGTACCTGGCATTGGATACG3780 
GGGTAAGGGAACCAAAAACGCTGGCATATTAACTGTTACATATGCCACAGAGTCACAACG3840 
CCAAAAATTTTTGGACACTGTTAAAATACCTTCTAGTGTACATGTTTCATTGGGTTACAT3900 
GACATTGTAAAGTATACTATGGATATTGTGTATGTATATTGTATACATACTACATAGATG3960 
ATATTATTGGTATTTTTGGTGTGGTTTGGTGTGTGTATATATATATGTTGCAATGTCCCG4020 
CTTTTGCCGTCTGTGCATGTGTGTGCGTATGTGTGGATAATTGTGTTTGTGTTTATTCTT4080 
ATACGTACCACACCATTGGAGGTGTTTTTTGTATATTTACTATTTTTTGTATTGCCCATG4140 
TGGTTGTTGCATAGACTGGCAATGGATATGATATAGTACTGTATATGTATGTGCATTGTG4200 
CATAACTACTGTACATAGCTTTTTATATTTTTTTTTGTTACTAATAAACATGGTTTCCCA4260 
CCGTGCTGCCAGGCGTAAGCGTGCATCTGCAACTGACCTATATAGAACCTGTAAACAATC4320 
GGGTACCTGTCCACCAGACGTTGTTGATAAAGTTGAGGGTACTACACTTGCTGACAAAAT4380 
TTTACAGTGGACTAGTTTAGGTATATTTTTGGGTGGGTTAGGCATAGGCACAGGTACTGG4440 
TACTGGGGGACGCACAGGATATATACCCCTGGGGGGTAGGCCTAATACTGTTGTAGATGT4500 
GTCTCCTGCACGTCCACCTGTAGTTATTGAACCTGTTGGTCCTTCTGAGCCATCTATTGT4560 
GCAATTGGTGGAGGACTCAAGTGTTATAACCTCTGGAACACCAGTACCAACATTTACAGG4620 
CACCTCTGGATTTGAAATTACTTCTTCTTCTACTACTACGCCTGCGGTATTGGATATTAC4680 
ACCCTCCTCTGGGTCTGTACAAATAACCTCTACTAGTTATACTAACCCTGCCTTTACGGA4740 
TCCTTCCTTAATTGAGGTTCCCCAAACAGGTGAAACCTCGGGTAATATATTTGTCAGTAC4800 
CCCTACATCAGGTACACATGGCTATGAGGAAATACCTATGGAAGTGTTTGCCACACATGG4860 
CACAGGTACCGAACCTATTAGCAGCACACCTACACCTGGAATCAGTCGTGTGGCAGGACC4920 
ACGTTTATATAGTAGAGCACATCAGCAGGTTCGTGTTAGTAATTTTGATTTTGTAACTCA4980 
CCCTTCATCATTTGTAACATTTGATAATCCTGCTTTTGAGCCTGTTGATACTACATTAAC5040 
ATATGAAGCTGCTGACATAGCTCCAGATCCGGATTTTCTGGACATTGTTCGTTTACATAG5100 
GCCTGCCTTAACCTCGCGTAAAGGAACAGTAAGGTTTAGTAGGCTTGGCAAAAAGGCTAC5160 
CATGGTTACCCGGCGTGGCACACAAATTGGAGCGCAAGTACATTATTACCATGACATTAG5220 
TAGTATTGCTCCTGCTGAAAGCATTGAATTACAGCCCCTAGTTCACGCTGAGCCCTCTGA5280 
TGCTTCAGATGCATTATTTGATATATATGCTGATGTGGACAATAACACATATTTAGATAC5340 
TGCATTTAATAATACAAGGGATTCGGGCACTACATATAACACAGGCTCACTACCTTCTGT5400 
GGCTTCTTCAGCATCTACTAAATATGCCAATACAACTATTCCTTTTAGTACCTCATGGAA5460 
TATGCCTGTAAATACTGGTCCTGATATTGCTTTACCAAGTACTACTCCACAGTTGCCATT5520 
GGTGCCTTCTGGACCAATAGACACAACATATGCAATAACCATTCAGGGTTCCAATTATTA5580 
TTTGTTGCCATTATTGTATTTTTTCCTAAAAAAACGTAAACGTATTCCCTATTTTTTTTC5640 
AGATGGCTATGTGGCGGTCTAGTGACAGCATGGTGTATTTGCCTCCACCTTCTGTGGCGA5700 
AGGTTGTCAATACTGATGATTATGTTACACGCACAGGCATATATTATTATGCTGGCAGCT5760 
CTAGATTATTAACAGTAGGACATCCATATTTTAAAGTGGGTATGAATGGTGGTCGCAAGC5820 
AGGACATTCCAAAGGTGTCTGCATATCAATATAGGGTATTTCGCGTGACATTGCCCGATC5880 
CTAATAAATTCAGTATTCCAGATGCATCCTTATATAATCCAGAAACACAACGTTTAGTAT5940 
GGGCTTGTGTAGGGGTGGAGGTGGGCAGGGGCCAGCCATTGGGTGTTGGTATTAGTGGAC6000 
ACCCATTATATAATAGACAGGATGATACTGAAAACTCACCATTTTCATCAACCACCAATA6060 
AGGACAGTAGGGATAATGTGTCTGTGGATTATAAACAGACACAGTTGTGCATTATAGGCT6120 
GTGTTCCCGCCATTGGGGAGCACTGGGGTAAGGGAAAGGCATGCAAGCCCAATAATGTAT6180 
CTACGGGGGACTGTCCTCCTTTGGAACTAGTAAACACCCCTATTGAGGATGGTGATATGA6240 
TTGATACTGGCTATGGAGCTATGGACTTTGGTGCATTGCAGGAAACCAAAAGTGAGGTGC6300 
CTTTAGATATTTGTCAATCCATTTGTAAATATCCTGATTATTTGCAAATGTCTGCAGATG6360 
TGTATGGGGACAGTATGTTCTTCTGTTTACGTAGGGAACAACTGTTTGCAAGACATTTTT6420 
GGAATCGTGGTGGTATGGTGGGTGACGCCATTCCTGCCCAATTGTATATTAAGGGCACAG6480 
ATATACGTGCAAACCCCGGTAGTTCTGTATACTGCCCCTCTCCCAGCGGTTCCATGGTAA6540 
CCTCTGATTCCCAGTTATTTAATAAGCCTTATTGGCTACATAAGGCCCAGGGCCACAACA6600 
ATGGTATATGTTGGCATAATCAATTATTTCTTACTGTTGTGGACACTACCCGTAGTACCA6660 
ACTTTACATTATCTACCTCTATAGAGTCTTCCATACCTTCTACATATGATCCTTCTAAGT6720 
TTAAGGAATATACCAGGCACGTGGAGGAGTATGATTTACAATTTATATTTCAACTGTGTA6780 
CTGTCACATTAACAACTGATGTTATGTCTTATATTCACACTATGAATTCCTCTATATTGG6840 
ACAATTGGAATTTTGCTGTAGCTCCTCCACCATCTGCCAGTTTGGTAGACACTTACAGAT6900 
ACCTACAGTCTGCAGCCATTACATGTCAAAAGGATGCTCCAGCACCTGAAAAGAAAGATC6960 
CATATGACGGTCTAAAGTTTTGGAATGTTGACTTAAGGGAAAAGTTTAGTTTGGAACTTG7020 
ATCAATTCCCTTTGGGACGTAAATTTTTGTTGCAGGCCAGGGTCCGCAGGCGCCCTACTA7080 
TAGGTCCCCGAAAGCGGCCTGCTGCATCCACTTCCTCGTCCTCAGCTACTAAACACAAAC7140 
GTAAACGTGTGTCTAAATAATGCATGTGTATGCCTTGTTATGTGTGTGTATGTTGTTTGT7200 
TTCCTTATGTGTTGAGTGTATATGTGTATGTTTGTAGGTATGTGTGTATATGTTTTTGTT7260 
AATAAAGTATGTATGACAGTTTCATGTGTGATTGCACACCCTGTGACTAACAGTGTATTT7320 
GTTTTACATATAATAGGTCTGCAACATTTCATACATAATCTATATGCCCTACCCTAAGGT7380 
GTGTTTACTACCTAATATGTAATTTTTACATTGTTGTATGCGTTTCTACATTTTATACTT7440 
CGCCATTTTGTGGCGACCGAAGTCGGTCGTGGGTTGAGCATTTTTTTTAAACTAGTGGAA7500 
ACCACCTTTCTCAGCAAAAACATGTCTTTACCTTAGGTTCACCCTGCATAGTTGGCACTG7560 
GTAACAGTTTTACTGGCGCGCCTTATTACTCATCATCCTGTCCAGGTGCACTGCAACAAT7620 
ACTTTGGCAACATCCATATCTCCACCCTATGTAATAAAACTGCTTTTAGGCATATATTTT7680 
AGCTGTTTTTACTTGCTTAATTAAATAGTTGGCCTGTATAACTACTTTTTGATTCAGGAA7740 
TGTGTCTTACAGTATAAGTTATACAAGTGACTAATGTAGCACACAATAGTTTATGCAACC7800 
GAAATAGGTTGGGCATACATACCTATACTTTTA7833 
(2) INFORMATION FOR SEQ ID NO:10: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 15 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: single 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: DNA (genomic) 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:10: 
TGTACATTGTGTCAT15 
(2) INFORMATION FOR SEQ ID NO:11: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 15 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: single 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: DNA (genomic) 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:11: 
AGCACATACTATACT15 
__________________________________________________________________________