Molecular mimicry of human cytokine and cytokine response pathway genes by KSHV

Science

Volumn 274, Issue 5293, 1996, Pages 1739-1744

  Moore, Patrick S ^a   Boshoff, Chris ^b   Weiss, Robin A ^b   Chang, Yuan ^a  

^a Columbia University ^*  (United States)

^b INSTITUTE OF CANCER RESEARCH   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

INTERFERON; INTERLEUKIN 6; MACROPHAGE INFLAMMATORY PROTEIN 1; VIRUS PROTEIN;

ARTICLE; CYTOKINE RESPONSIVE ELEMENT; HERPES VIRUS; KAPOSI SARCOMA; PRIORITY JOURNAL; STRAIN DIFFERENCE; VIRUS EXPRESSION; VIRUS REPLICATION; VIRUS TRANSMISSION;

AMINO ACID SEQUENCE; ANIMALS; CELL DIVISION; CELL LINE; GENE EXPRESSION; GENES, VIRAL; HERPESVIRUS 4, HUMAN; HERPESVIRUS 8, HUMAN; HIV-1; HUMANS; INTERLEUKIN-6; LYMPH NODES; LYMPHOMA, B-CELL; MACROPHAGE INFLAMMATORY PROTEIN-1; MICE; MOLECULAR MIMICRY; MOLECULAR SEQUENCE DATA; RECEPTORS, CCR5; RECEPTORS, CYTOKINE; RECEPTORS, HIV; SARCOMA, KAPOSI; SEQUENCE ALIGNMENT; SIGNAL TRANSDUCTION; TETRADECANOYLPHORBOL ACETATE; TUMOR CELLS, CULTURED; VIRAL NONSTRUCTURAL PROTEINS; VIRUS REPLICATION;

HERPES; HERPESVIRIDAE; HUMAN HERPESVIRUS 8; HUMAN IMMUNODEFICIENCY VIRUS 1;

EID: 0029837991     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.274.5293.1739     Document Type: Article

References (82)

1. Y. Chang et al., Science 265, 1865 (1994).
2. P. S. Moore et al., Virology 70, 549 (1996).
3. C. Boshoff et al., Lancet 345, 1043 (1995); P. S. Moore and Y. Chang, N. Engl. J. Med. 332, 1181 (1996); M. Schalling et al., Nature Med. 1, 707 (1995); Y. Chang et al., Archiv. Int Med 156, 202 (1996).
4. C. Boshoff et al., Lancet 345, 1043 (1995); P. S. Moore and Y. Chang, N. Engl. J. Med. 332, 1181 (1996); M. Schalling et al., Nature Med. 1, 707 (1995); Y. Chang et al., Archiv. Int Med 156, 202 (1996).
5. C. Boshoff et al., Lancet 345, 1043 (1995); P. S. Moore and Y. Chang, N. Engl. J. Med. 332, 1181 (1996); M. Schalling et al., Nature Med. 1, 707 (1995); Y. Chang et al., Archiv. Int Med 156, 202 (1996).
6. C. Boshoff et al., Lancet 345, 1043 (1995); P. S. Moore and Y. Chang, N. Engl. J. Med. 332, 1181 (1996); M. Schalling et al., Nature Med. 1, 707 (1995); Y. Chang et al., Archiv. Int Med 156, 202 (1996).
7. N. Dupin et al., Lancet 345, 761 (1995).
8. C. Boshoff et al., Nature Med. 1, 1274 (1995); W. Zhong, H. Wang, B. Herndier, D. Ganem, Proc. Natl. Acad. Sci. U.S.A. 93, 6641 (1996).
9. C. Boshoff et al., Nature Med. 1, 1274 (1995); W. Zhong, H. Wang, B. Herndier, D. Ganem, Proc. Natl. Acad. Sci. U.S.A. 93, 6641 (1996).
10. G. Miller et al., N. Engl. J. Med. 334, 1292 (1996); D. H. Kedes et al., Nature Med. 2, 918 (1996); G. R. Simpson et al., Lancet 348, 1133 (1996); E. T. Lennette, B. J. Blackbourne, J. A. Levy, ibid., p. 858.
11. G. Miller et al., N. Engl. J. Med. 334, 1292 (1996); D. H. Kedes et al., Nature Med. 2, 918 (1996); G. R. Simpson et al., Lancet 348, 1133 (1996); E. T. Lennette, B. J. Blackbourne, J. A. Levy, ibid., p. 858.
12. G. Miller et al., N. Engl. J. Med. 334, 1292 (1996); D. H. Kedes et al., Nature Med. 2, 918 (1996); G. R. Simpson et al., Lancet 348, 1133 (1996); E. T. Lennette, B. J. Blackbourne, J. A. Levy, ibid., p. 858.
13. G. Miller et al., N. Engl. J. Med. 334, 1292 (1996); D. H. Kedes et al., Nature Med. 2, 918 (1996); G. R. Simpson et al., Lancet 348, 1133 (1996); E. T. Lennette, B. J. Blackbourne, J. A. Levy, ibid., p. 858.
14. S.-J. Gao et al., Nature Med. 2, 925 (1996).
15. S.-J. Gao et al., N. Engl. J. Med. 335, 233 (1996).
16. V. Beral, Cancer Surveys 10, 5 (1991); T. A. Peterman, H. W. Jaffe, V. Beral, AIDS 7, 605 (1993); R. A. Weiss, Nature Med. 2, 277 (1996); J. J. O'Leary, ibid., p. 862.
17. V. Beral, Cancer Surveys 10, 5 (1991); T. A. Peterman, H. W. Jaffe, V. Beral, AIDS 7, 605 (1993); R. A. Weiss, Nature Med. 2, 277 (1996); J. J. O'Leary, ibid., p. 862.
18. V. Beral, Cancer Surveys 10, 5 (1991); T. A. Peterman, H. W. Jaffe, V. Beral, AIDS 7, 605 (1993); R. A. Weiss, Nature Med. 2, 277 (1996); J. J. O'Leary, ibid., p. 862.
19. V. Beral, Cancer Surveys 10, 5 (1991); T. A. Peterman, H. W. Jaffe, V. Beral, AIDS 7, 605 (1993); R. A. Weiss, Nature Med. 2, 277 (1996); J. J. O'Leary, ibid., p. 862.
20. E. Cesarman, Y. Chang, P. S. Moore, J. W. Said, D. M. Knowles, N. Engl. J. Med. 332, 1186 (1995); J. Soulier et al., Blood 86, 1276 (1995); A. Gessain et al., ibid. 87, 414 (1996); M. Corbellino et al., Clin. Infect. Dis. 22, 1120 (1996).
21. E. Cesarman, Y. Chang, P. S. Moore, J. W. Said, D. M. Knowles, N. Engl. J. Med. 332, 1186 (1995); J. Soulier et al., Blood 86, 1276 (1995); A. Gessain et al., ibid. 87, 414 (1996); M. Corbellino et al., Clin. Infect. Dis. 22, 1120 (1996).
22. E. Cesarman, Y. Chang, P. S. Moore, J. W. Said, D. M. Knowles, N. Engl. J. Med. 332, 1186 (1995); J. Soulier et al., Blood 86, 1276 (1995); A. Gessain et al., ibid. 87, 414 (1996); M. Corbellino et al., Clin. Infect. Dis. 22, 1120 (1996).
23. E. Cesarman, Y. Chang, P. S. Moore, J. W. Said, D. M. Knowles, N. Engl. J. Med. 332, 1186 (1995); J. Soulier et al., Blood 86, 1276 (1995); A. Gessain et al., ibid. 87, 414 (1996); M. Corbellino et al., Clin. Infect. Dis. 22, 1120 (1996).
24. Genomic inserts were randomly sheared, cloned into M13mp18, and sequenced to greater than 12-fold average redundancy with complete bidirectional sequencing. Details of KSHV genomic sequencing are reported in J. J. Russo et al., Proc. Natl. Acad. Sci. U.S.A. 93, 14862 (1996). The descriptive nomenclature of KSHV genes is based on the naming system derived for herpesvirus saimiri [J.-C. Albrecht et al., J. Virol. 66, 5047 (1992)].
25. Genomic inserts were randomly sheared, cloned into M13mp18, and sequenced to greater than 12-fold average redundancy with complete bidirectional sequencing. Details of KSHV genomic sequencing are reported in J. J. Russo et al., Proc. Natl. Acad. Sci. U.S.A. 93, 14862 (1996). The descriptive nomenclature of KSHV genes is based on the naming system derived for herpesvirus saimiri [J.-C. Albrecht et al., J. Virol. 66, 5047 (1992)].
26. E. Cesarman et al., Blood 86, 2708 (1995).
27. 8).
28. 8).
29. A hypothetical protein with conserved cysteine motifs similar to β-chemokine motif signatures has recently been reported in the molluscum contagiosum virus (MCV) genome [T. G. Senkevich et al., Science 273, 813 (1996)]. Neither vMIP-I or vMIP-II have significant similarity to the MCV protein.
30. Amino acid sequences were aligned by CLUSTAL W [J. D. Thompson, D. G. Higgins, T. J. Gibson, Nucl. Acids Res. 22, 4673 (1994)] and compared by means of PAUP 3.1.1. Both rooted and unrooted bootstrap comparisons produced phylogenetic trees having all 100 bootstrap replicates with viral homologs being less divergent from each other than from the human homologs. The authors thank S. Olsen for performing the parsimony analysis.
31. Northern blotting was performed under standard conditions with random-labeled probes (1) derived from PCR products for the following primer sets: vMIP-1: 5′-AGC ATA TAA GGA ACT CGG CGT TAC-3′, 5′-GGT AGA TAA ATC CCC CCC CTT TG-3′; vMIP-II: 5′-TGC ATC AGC TTC TTC ACC CAG-3′, 5′-TGC TGT CTC GGT TAG CAG AAA AG-3′; vIL-6: 5′-TCA CGT CGC TCT TTA CTT ATC GTG-3′, 5′-CGC CCT TCAGTG AGA CTT CGT AAC-3′; vIRF: 5′-CTT GCG ATG AAC CAT CCA GG-3′, 5′-ACA ACA CCC AAT TCC CCG TC-3′ on total cell RNA extracted with RNAzol according to manufacturer's instructions (TelTest Inc., Friendswood, TX) and 10 μg of total RNA was loaded in each lane. BCP-1, BC-1, and P3HR1 were maintained in culture conditions and induced with TPA as described (8). PCR amplification for these viral genes was performed with the vMIP-I, vMIP-II, vIL-6, and vIRF primer sets in 35 amplification cycles and compared to dilutions of whole BC-1 DNA as a positive control; PCR conditions were as described [P. S. Moore and Y. Chang, N. Engl. J. Med. 332, 1181 (1996)]. DNA from KS spindle cell lines used for these experiments was described in M. Dictor, E. Rambech, D. Way, M. Witte, N. Bendsöe, Am. J. Pathol. 148, 2009 (1996) and kindly provided by M. Dictor, D. Way, and M. Witte. Amplifiability of DNA samples was confirmed with human HLA-DQ α and pyruvate dehydrogenase primers.
32. J. A. Strauchen et al., Ann. Intern. Med. 125, 822 (1996). Peripheral lymphocytes from the patient whose PEL tumor is shown in Fig. 4C were used to originate the BCP-1 cell line (7).
33. O. Flore, S.-J. Gao, P. S. Moore, unpublished observation.
34. B. Ensoli et al., nature 371, 674 (1994); S.A. Miles, Cancer Treatment Res. 63, 129 (1992).
35. B. Ensoli et al., nature 371, 674 (1994); S.A. Miles, Cancer Treatment Res. 63, 129 (1992).
36. J. A. Ambroziak et al., Science 268, 582 (1995); C. Lebbé et al., Lancet 345, 1180 (1995); M. Dictor, E. Rambech, D. Way, M. Witte, N. Bendsöe, Am. J. Pathol. 148, 2009 (1996); L. Flamand, R. A. Zeman, J. L. Bryant, Y. Lunardi-lskandar, R. C. Gallo, J. AIDS Hum. Retrovirol. 15, 194 (1996).
37. J. A. Ambroziak et al., Science 268, 582 (1995); C. Lebbé et al., Lancet 345, 1180 (1995); M. Dictor, E. Rambech, D. Way, M. Witte, N. Bendsöe, Am. J. Pathol. 148, 2009 (1996); L. Flamand, R. A. Zeman, J. L. Bryant, Y. Lunardi-lskandar, R. C. Gallo, J. AIDS Hum. Retrovirol. 15, 194 (1996).
38. J. A. Ambroziak et al., Science 268, 582 (1995); C. Lebbé et al., Lancet 345, 1180 (1995); M. Dictor, E. Rambech, D. Way, M. Witte, N. Bendsöe, Am. J. Pathol. 148, 2009 (1996); L. Flamand, R. A. Zeman, J. L. Bryant, Y. Lunardi-lskandar, R. C. Gallo, J. AIDS Hum. Retrovirol. 15, 194 (1996).
39. J. A. Ambroziak et al., Science 268, 582 (1995); C. Lebbé et al., Lancet 345, 1180 (1995); M. Dictor, E. Rambech, D. Way, M. Witte, N. Bendsöe, Am. J. Pathol. 148, 2009 (1996); L. Flamand, R. A. Zeman, J. L. Bryant, Y. Lunardi-lskandar, R. C. Gallo, J. AIDS Hum. Retrovirol. 15, 194 (1996).
40. The vIL-6 was cloned from a 695-bp polymerase chain reaction product with the primer set described (16) and amplified for 35 cycles with 0.1 μg of BC-1 DNA as a template. PCR product was initially cloned into PCR-Script (Stratagene, La Jolla, CA) from which an EcoRV insert was then cloned into the pMET7 expression vector [Y. Takebe et al., mol. Cell. Biol. 8, 466 (1988); kindly provided by J. Culpepper] and transfected by means of DEAE-dextran plus chloroquine into COS7 cells (CRL-1651, American Type Culture Collection, Rockville, MD). The EcoRV insert was also cloned into the pMET7 vector in the reverse orientation (6-LIv) relative to the SRα promoter as a negative control, with orientation and sequence fidelity of both constructs confirmed by bidirectional sequencing by means of dye-primer chemistry on an ABI 377 sequenator (Applied Biosystems Inc., Foster City, CA).
41. Serum-free COS7 supernatants (15 ml) were concentrated to 1.5 ml by Ultrafiltration with a Centriplus 10 filter (Amicon, Beverly, MA) and 100 μl of supernatant concentrate or 1 μg of rhulL-6 (R&D Systems, Minneapolis, MN) was loaded per each lane in Laemmeli buffer. For cell lysate immunoblotting, exponential phase cells with and without TPA (20 ng/ml) induction for 48 hours were pelleted and 100 μg of whole protein cell protein solubilized in Laemmeli buffer was loaded per lahe, separated by electrophoresis on a 15% SDS-polyacrylamide gel and immunoblotted and developed by means of standard conditions (8) with either rabbit antipeptide antibody (1:100-1:1000 dilution) or anti-hulL-6 (1 μg per milliliter; R&D Systems, Minneapolis, MN).
42. 3H-thymidine in 1 ml IMDM) added to each well during the final 4 hours of incubation. Cells were harvested and incorporation of 3H-thymidine determined with a liquid scintillation counter. Each data point is the average of six determinations with standard deviations shown.
43. 2 in PBS by standard immunohistochemical protocols available from authors. The primary antibody was applied at a dilution of 1:1250 after blocking with 10% normal goat serum, 1% BSA, 0.5% Tween 20 and developed with diamino-benzidine (DAB) chromogen. Amino ethyl carbazole (AEC) or Vector Red staining was also used to better discriminate double-labeled cells, with Fast Blue counterstaining for some surface antigens. Cell antigens were examined with the following antibodies: CD68 (1:800, from clone Kim 6 kindly provided by G. Cattoretti and visualized by fluorescein-rhodamine double-labeling), epithelial membrane antigen (EMA, 1:500, Dako, Carpinteria, CA), CD3 (1:200, Dako), CD20 (1:200, Dako), OPD4 (1:100, Dako), CD34 (1:15, Dako), CD45 (1:400, from clone 9.4 kindly provided by G. Cattoretti), L26 (1:100, Immunotech, Westbrook, ME) and Leu22 (1:100, Becton-Dickinson, San Jose, CA) on tissues prepared according to manufacturer's instructions. Specific vIL-6 colocalization was only found with CD34 and CD45 in KS lesions, EMA in PEL, and CD20 and CD45 in lymph node tissues. The authors thank L. Ward for extensive help in immunohistochemistry preparations.
44. Immunohistochemical vIL-6 localization was performed on exponential phase BCP-1 cells with or without 48-hour TPA incubation after embedding in 1% agar in saline. The percentages of positive cells were determined from cell counts of three random high power microscopic fields per slide. Lower percentages of BCP-1 cells stain positively for vIL-6 after TPA treatment possibly reflecting cell lysis and death from lytic virus replication induction by TPA. The vIL-6 immunostaining of both cells and tissues was confirmed by neutralization after overnight incubation of antisera with vIL-6 synthetic peptides (0.1 ?g/ml) at 4°C and with preimmune rabbit antisera run in parallel to the postimmune immunostaining. No specific staining was seen after either peptide neutralization or use of preimmune sera.
45. W. Zhong, H. Wang, B. Herndier, D. Ganem, Proc. Natl. Acad. Sci. U.S.A. 93, 6641 (1996).
46. F. Cocchi et al., Science 270, 1811 (1995); T. Dragic et al., Nature 381, 667 (1996); H. Deng et al., ibid., p. 661.
47. F. Cocchi et al., Science 270, 1811 (1995); T. Dragic et al., Nature 381, 667 (1996); H. Deng et al., ibid., p. 661.
48. F. Cocchi et al., Science 270, 1811 (1995); T. Dragic et al., Nature 381, 667 (1996); H. Deng et al., ibid., p. 661.
49. 50 of SF162, M23, or ROD/B virus culture stock was added. Cells were washed four times after 4 hours of virus incubation and grown in DMEM with 5% FBS for 72 hours before immunostaining for HIV-1 p24 or HIV-2 gp105. Each condition was replicated three to four times with medians and error bars representing the standard deviations expressed as percentages of the foci formed in the presence of CCR5 alone.
50. G. Simmons et al., J. Virol. 70, 8355 (1996); P. R. Clapham, A. McKnight, R. A. Weiss, J. Virol. 66, 3531 (1992).
51. G. Simmons et al., J. Virol. 70, 8355 (1996); P. R. Clapham, A. McKnight, R. A. Weiss, J. Virol. 66, 3531 (1992).
52. P. M. Murphy, Infect. Agents Dis. 3, 137 (1994); T. G. Senkevich et al., Science 273, 813 (1996); J.-C. Albrecht et al., J. Virol. 66, 5047 (1992); J. L. Gao and P. M. Murphy, J. Biol. Chem. 269, 28539 (1994); M. S. Chee et al., Curr. Top. Microbiol. Immunol. 154, 125 (1990); R. F. Massung et al., Virology 201, 215 (1994).
53. P. M. Murphy, Infect. Agents Dis. 3, 137 (1994); T. G. Senkevich et al., Science 273, 813 (1996); J.-C. Albrecht et al., J. Virol. 66, 5047 (1992); J. L. Gao and P. M. Murphy, J. Biol. Chem. 269, 28539 (1994); M. S. Chee et al., Curr. Top. Microbiol. Immunol. 154, 125 (1990); R. F. Massung et al., Virology 201, 215 (1994).
54. P. M. Murphy, Infect. Agents Dis. 3, 137 (1994); T. G. Senkevich et al., Science 273, 813 (1996); J.-C. Albrecht et al., J. Virol. 66, 5047 (1992); J. L. Gao and P. M. Murphy, J. Biol. Chem. 269, 28539 (1994); M. S. Chee et al., Curr. Top. Microbiol. Immunol. 154, 125 (1990); R. F. Massung et al., Virology 201, 215 (1994).
55. P. M. Murphy, Infect. Agents Dis. 3, 137 (1994); T. G. Senkevich et al., Science 273, 813 (1996); J.-C. Albrecht et al., J. Virol. 66, 5047 (1992); J. L. Gao and P. M. Murphy, J. Biol. Chem. 269, 28539 (1994); M. S. Chee et al., Curr. Top. Microbiol. Immunol. 154, 125 (1990); R. F. Massung et al., Virology 201, 215 (1994).
56. P. M. Murphy, Infect. Agents Dis. 3, 137 (1994); T. G. Senkevich et al., Science 273, 813 (1996); J.-C. Albrecht et al., J. Virol. 66, 5047 (1992); J. L. Gao and P. M. Murphy, J. Biol. Chem. 269, 28539 (1994); M. S. Chee et al., Curr. Top. Microbiol. Immunol. 154, 125 (1990); R. F. Massung et al., Virology 201, 215 (1994).
57. P. M. Murphy, Infect. Agents Dis. 3, 137 (1994); T. G. Senkevich et al., Science 273, 813 (1996); J.-C. Albrecht et al., J. Virol. 66, 5047 (1992); J. L. Gao and P. M. Murphy, J. Biol. Chem. 269, 28539 (1994); M. S. Chee et al., Curr. Top. Microbiol. Immunol. 154, 125 (1990); R. F. Massung et al., Virology 201, 215 (1994).
58. R. Sarid, T. Sato, R. Bohenzky, J. Russo, Y. Chang, in preparation; E. Cesarman et al., J. Virol. 70, 8218 (1996); Y. Chang et al., Nature 382, 410 (1996); R. Sarid, P. S. Moore, Y. Chang, unpublished observation.
59. R. Sarid, T. Sato, R. Bohenzky, J. Russo, Y. Chang, in preparation; E. Cesarman et al., J. Virol. 70, 8218 (1996); Y. Chang et al., Nature 382, 410 (1996); R. Sarid, P. S. Moore, Y. Chang, unpublished observation.
60. R. Sarid, T. Sato, R. Bohenzky, J. Russo, Y. Chang, in preparation; E. Cesarman et al., J. Virol. 70, 8218 (1996); Y. Chang et al., Nature 382, 410 (1996); R. Sarid, P. S. Moore, Y. Chang, unpublished observation.
61. R. Sarid, T. Sato, R. Bohenzky, J. Russo, Y. Chang, in preparation; E. Cesarman et al., J. Virol. 70, 8218 (1996); Y. Chang et al., Nature 382, 410 (1996); R. Sarid, P. S. Moore, Y. Chang, unpublished observation.
62. M. L. Cleary, S. D. Smith, J. Sklar, Cell 47, 19 (1986); I. Palmero et al., Oncogene 8, 1049 (1993); C. Larcher et al., Eur. J. Immunol. 25, 1713 (1995); M. Birkenbach, K. Josefsen, R. Yalamanchili, G. Lenoir, E. Kieff, J. Virol. 67, 2209 (1993).
63. M. L. Cleary, S. D. Smith, J. Sklar, Cell 47, 19 (1986); I. Palmero et al., Oncogene 8, 1049 (1993); C. Larcher et al., Eur. J. Immunol. 25, 1713 (1995); M. Birkenbach, K. Josefsen, R. Yalamanchili, G. Lenoir, E. Kieff, J. Virol. 67, 2209 (1993).
64. M. L. Cleary, S. D. Smith, J. Sklar, Cell 47, 19 (1986); I. Palmero et al., Oncogene 8, 1049 (1993); C. Larcher et al., Eur. J. Immunol. 25, 1713 (1995); M. Birkenbach, K. Josefsen, R. Yalamanchili, G. Lenoir, E. Kieff, J. Virol. 67, 2209 (1993).
65. M. L. Cleary, S. D. Smith, J. Sklar, Cell 47, 19 (1986); I. Palmero et al., Oncogene 8, 1049 (1993); C. Larcher et al., Eur. J. Immunol. 25, 1713 (1995); M. Birkenbach, K. Josefsen, R. Yalamanchili, G. Lenoir, E. Kieff, J. Virol. 67, 2209 (1993).
66. G. Tosato, J. Tanner, K. D. Jones, M. Revel, S. E. Pike, J. Virol. 64, 3033 (1990).
67. Y. Shen and T. E. Shenk, Curr. Opin. Gen. Dev. 5, 105 (1995); K. H. Vousden, Sem. Cancer Biol. 6, 109 (1995); L. J. Appleman and A. B. Frey, Int. J. Cancer 63, 576 (1995).
68. Y. Shen and T. E. Shenk, Curr. Opin. Gen. Dev. 5, 105 (1995); K. H. Vousden, Sem. Cancer Biol. 6, 109 (1995); L. J. Appleman and A. B. Frey, Int. J. Cancer 63, 576 (1995).
69. Y. Shen and T. E. Shenk, Curr. Opin. Gen. Dev. 5, 105 (1995); K. H. Vousden, Sem. Cancer Biol. 6, 109 (1995); L. J. Appleman and A. B. Frey, Int. J. Cancer 63, 576 (1995).
70. A. Lichtenstein, Y. Tu, C. Fady, R. Vescio, J. Berenson, Cell. Immunol. 162, 248 (1995).
71. C. Holzinger et al., Immunol. Lett. 35, 109 (1993).
72. A. Lafeuillade, G. Kaplanski, T. Allegre, J. P. de Jaureguiberry, J. AIDS Hum. Retrovirol. 12, 95 (1996); T. Cohen, D. Nahari, L. W. Cerem, G. Neufeld, B.-Z. Levi, J. Biol. Chem. 271, 736 (1996).
73. A. Lafeuillade, G. Kaplanski, T. Allegre, J. P. de Jaureguiberry, J. AIDS Hum. Retrovirol. 12, 95 (1996); T. Cohen, D. Nahari, L. W. Cerem, G. Neufeld, B.-Z. Levi, J. Biol. Chem. 271, 736 (1996).
74. G. Scala et al., J. Exp. Med. 172, 61 (1990).
75. H. Harada et al., Science 259, 971 (1993).
76. A M. Hardy, J. AIDS 4, 386 (1991); G. F. Lemp, S. F. Payne, D. Neal, T. Temelso, G. W. Rutherford, J. Am. Med. Assoc. 263, 402 (1990); R. Rothenberg et al., N. Engl. J. Med. 317, 1297 (1987); L. P. Jacobson et al., Am. J. Epidemiol. 138, 953 (1993); J. D. Lundgren, M. Melbye, C. Pederson, P. S. Rosenberg, J. Gerstoft, ibid. 141, 652 (1995).
77. A M. Hardy, J. AIDS 4, 386 (1991); G. F. Lemp, S. F. Payne, D. Neal, T. Temelso, G. W. Rutherford, J. Am. Med. Assoc. 263, 402 (1990); R. Rothenberg et al., N. Engl. J. Med. 317, 1297 (1987); L. P. Jacobson et al., Am. J. Epidemiol. 138, 953 (1993); J. D. Lundgren, M. Melbye, C. Pederson, P. S. Rosenberg, J. Gerstoft, ibid. 141, 652 (1995).
78. A M. Hardy, J. AIDS 4, 386 (1991); G. F. Lemp, S. F. Payne, D. Neal, T. Temelso, G. W. Rutherford, J. Am. Med. Assoc. 263, 402 (1990); R. Rothenberg et al., N. Engl. J. Med. 317, 1297 (1987); L. P. Jacobson et al., Am. J. Epidemiol. 138, 953 (1993); J. D. Lundgren, M. Melbye, C. Pederson, P. S. Rosenberg, J. Gerstoft, ibid. 141, 652 (1995).
79. A M. Hardy, J. AIDS 4, 386 (1991); G. F. Lemp, S. F. Payne, D. Neal, T. Temelso, G. W. Rutherford, J. Am. Med. Assoc. 263, 402 (1990); R. Rothenberg et al., N. Engl. J. Med. 317, 1297 (1987); L. P. Jacobson et al., Am. J. Epidemiol. 138, 953 (1993); J. D. Lundgren, M. Melbye, C. Pederson, P. S. Rosenberg, J. Gerstoft, ibid. 141, 652 (1995).
80. A M. Hardy, J. AIDS 4, 386 (1991); G. F. Lemp, S. F. Payne, D. Neal, T. Temelso, G. W. Rutherford, J. Am. Med. Assoc. 263, 402 (1990); R. Rothenberg et al., N. Engl. J. Med. 317, 1297 (1987); L. P. Jacobson et al., Am. J. Epidemiol. 138, 953 (1993); J. D. Lundgren, M. Melbye, C. Pederson, P. S. Rosenberg, J. Gerstoft, ibid. 141, 652 (1995).
81. Abbreviations for the amino acid residues are: A, Ala; C, Cys; D, Asp; E, Glu; F, Phe; G, Gly; H, His; I, He; K, Lys; L, Leu; M, Met; N, Asn; P, Pro; Q, Gln; R, Arg; S, Ser: T, Thr; V, Val; W, Tip; and Y, Tyr.
82. The authors thank R. A. Bohenzky, J. Russo, and I. A. Edelman for collaborative work on genomic sequencing of KSHV; G. Simmons for help with HIV inhibition experiments, J. Strauchen for PEL tissue sections; Y.-Z. Cao, S. Silverstein, J. Luban and C. Parravicini for helpful discussions; R. Sarid, J. P. Parry, M. Yan, W. Zheng and A.-E. Thlick for technical assistance; and M. Davis and D. Holland for help in preparing the manuscript. Supported by NIH NCI grant CA67391, an award from the James S. McDonnell Foundation, the Cancer Research Campaign, and the Mercury Phoenix Trust.