Adaptive evolution of human immunodeficiency virus-type 1 during the natural course of infection

Science

Volumn 272, Issue 5261, 1996, Pages 537-542

  Wolinsky, Steven M ^b   Korber, Bette T M ^b   Neumann, Avidan U ^b   Daniels, Michael ^b   Kunstman, Kevin J ^b   Whetsell, Amy J ^b   Furtado, Manohar R ^b   Cao, Yunzhen ^b   Ho, David D ^b   Safrit, Jeffrey T ^b   Koup, Richard A ^b  

^a NORTHWESTERN UNIVERSITY   (United States)

^b NONE

Author keywords

[No Author keywords available]

Indexed keywords

CD4 ANTIGEN; EPITOPE;

AMINO ACID SEQUENCE; ARTICLE; BLOOD SAMPLING; CYTOTOXIC T LYMPHOCYTE; DISEASE COURSE; EVOLUTION; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; NATURAL SELECTION; NONHUMAN; PRIORITY JOURNAL; T LYMPHOCYTE;

EID: 15844385082     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.272.5261.537     Document Type: Article

References (101)

1. E. S Daar, T Mougdil, R. D. Meyer, D D. Ho, N. Engl. J. Med. 324, 961 (1991); C. Graziozi et al., Proc. Natl. Acad. Sci. U.S.A 90, 6405 (1993); M S. Saag et al , J Exp. Med. 172, 1055 (1991), S J. Clark et al., N. Engl. J. Med. 324, 954 (1991)
2. E. S Daar, T Mougdil, R. D. Meyer, D D. Ho, N. Engl. J. Med. 324, 961 (1991); C. Graziozi et al., Proc. Natl. Acad. Sci. U.S.A 90, 6405 (1993); M S. Saag et al , J Exp. Med. 172, 1055 (1991), S J. Clark et al., N. Engl. J. Med. 324, 954 (1991)
3. E. S Daar, T Mougdil, R. D. Meyer, D D. Ho, N. Engl. J. Med. 324, 961 (1991); C. Graziozi et al., Proc. Natl. Acad. Sci. U.S.A 90, 6405 (1993); M S. Saag et al , J Exp. Med. 172, 1055 (1991), S J. Clark et al., N. Engl. J. Med. 324, 954 (1991)
4. E. S Daar, T Mougdil, R. D. Meyer, D D. Ho, N. Engl. J. Med. 324, 961 (1991); C. Graziozi et al., Proc. Natl. Acad. Sci. U.S.A 90, 6405 (1993); M S. Saag et al , J Exp. Med. 172, 1055 (1991), S J. Clark et al., N. Engl. J. Med. 324, 954 (1991)
5. S M. Wolinsky et al , Science 255, 1134 (1992), T. Zhu et al., ibid. 261, 1179 (1993); L. Q. Zhang et al., J. Virol. 67, 3345 (1993); N Ahmed, B. M. Baroudy, R C. Baker, C. Drappy, ibid. 69, 1001 (1995); J. W. Mallors et al., Ann. Intern. Med 122, 573 (1995); E. C. Holmes, L. Q. Zang, P Simmonds, C. A Ludlam, A. J. Leigh-Brown, Proc Natl. Acad Sci. U.S A 89, 4835 (1992); B. T. M. Korber et al., AIDS Res Hum. Retroviruses 8, 1461 (1992); C L Kuiken et al., J. Virol. 66, 4622 (1992); T. F. W. Woffs, G. Zwart, M. Bakker, J. Goudsmit, Virology 189, 103 (1992).
6. S M. Wolinsky et al , Science 255, 1134 (1992), T. Zhu et al., ibid. 261, 1179 (1993); L. Q. Zhang et al., J. Virol. 67, 3345 (1993); N Ahmed, B. M. Baroudy, R C. Baker, C. Drappy, ibid. 69, 1001 (1995); J. W. Mallors et al., Ann. Intern. Med 122, 573 (1995); E. C. Holmes, L. Q. Zang, P Simmonds, C. A Ludlam, A. J. Leigh-Brown, Proc Natl. Acad Sci. U.S A 89, 4835 (1992); B. T. M. Korber et al., AIDS Res Hum. Retroviruses 8, 1461 (1992); C L Kuiken et al., J. Virol. 66, 4622 (1992); T. F. W. Woffs, G. Zwart, M. Bakker, J. Goudsmit, Virology 189, 103 (1992).
7. S M. Wolinsky et al , Science 255, 1134 (1992), T. Zhu et al., ibid. 261, 1179 (1993); L. Q. Zhang et al., J. Virol. 67, 3345 (1993); N Ahmed, B. M. Baroudy, R C. Baker, C. Drappy, ibid. 69, 1001 (1995); J. W. Mallors et al., Ann. Intern. Med 122, 573 (1995); E. C. Holmes, L. Q. Zang, P Simmonds, C. A Ludlam, A. J. Leigh-Brown, Proc Natl. Acad Sci. U.S A 89, 4835 (1992); B. T. M. Korber et al., AIDS Res Hum. Retroviruses 8, 1461 (1992); C L Kuiken et al., J. Virol. 66, 4622 (1992); T. F. W. Woffs, G. Zwart, M. Bakker, J. Goudsmit, Virology 189, 103 (1992).
8. S M. Wolinsky et al , Science 255, 1134 (1992), T. Zhu et al., ibid. 261, 1179 (1993); L. Q. Zhang et al., J. Virol. 67, 3345 (1993); N Ahmed, B. M. Baroudy, R C. Baker, C. Drappy, ibid. 69, 1001 (1995); J. W. Mallors et al., Ann. Intern. Med 122, 573 (1995); E. C. Holmes, L. Q. Zang, P Simmonds, C. A Ludlam, A. J. Leigh-Brown, Proc Natl. Acad Sci. U.S A 89, 4835 (1992); B. T. M. Korber et al., AIDS Res Hum. Retroviruses 8, 1461 (1992); C L Kuiken et al., J. Virol. 66, 4622 (1992); T. F. W. Woffs, G. Zwart, M. Bakker, J. Goudsmit, Virology 189, 103 (1992).
9. S M. Wolinsky et al , Science 255, 1134 (1992), T. Zhu et al., ibid. 261, 1179 (1993); L. Q. Zhang et al., J. Virol. 67, 3345 (1993); N Ahmed, B. M. Baroudy, R C. Baker, C. Drappy, ibid. 69, 1001 (1995); J. W. Mallors et al., Ann. Intern. Med 122, 573 (1995); E. C. Holmes, L. Q. Zang, P Simmonds, C. A Ludlam, A. J. Leigh-Brown, Proc Natl. Acad Sci. U.S A 89, 4835 (1992); B. T. M. Korber et al., AIDS Res Hum. Retroviruses 8, 1461 (1992); C L Kuiken et al., J. Virol. 66, 4622 (1992); T. F. W. Woffs, G. Zwart, M. Bakker, J. Goudsmit, Virology 189, 103 (1992).
10. S M. Wolinsky et al , Science 255, 1134 (1992), T. Zhu et al., ibid. 261, 1179 (1993); L. Q. Zhang et al., J. Virol. 67, 3345 (1993); N Ahmed, B. M. Baroudy, R C. Baker, C. Drappy, ibid. 69, 1001 (1995); J. W. Mallors et al., Ann. Intern. Med 122, 573 (1995); E. C. Holmes, L. Q. Zang, P Simmonds, C. A Ludlam, A. J. Leigh-Brown, Proc Natl. Acad Sci. U.S A 89, 4835 (1992); B. T. M. Korber et al., AIDS Res Hum. Retroviruses 8, 1461 (1992); C L Kuiken et al., J. Virol. 66, 4622 (1992); T. F. W. Woffs, G. Zwart, M. Bakker, J. Goudsmit, Virology 189, 103 (1992).
11. S M. Wolinsky et al , Science 255, 1134 (1992), T. Zhu et al., ibid. 261, 1179 (1993); L. Q. Zhang et al., J. Virol. 67, 3345 (1993); N Ahmed, B. M. Baroudy, R C. Baker, C. Drappy, ibid. 69, 1001 (1995); J. W. Mallors et al., Ann. Intern. Med 122, 573 (1995); E. C. Holmes, L. Q. Zang, P Simmonds, C. A Ludlam, A. J. Leigh-Brown, Proc Natl. Acad Sci. U.S A 89, 4835 (1992); B. T. M. Korber et al., AIDS Res Hum. Retroviruses 8, 1461 (1992); C L Kuiken et al., J. Virol. 66, 4622 (1992); T. F. W. Woffs, G. Zwart, M. Bakker, J. Goudsmit, Virology 189, 103 (1992).
12. S M. Wolinsky et al , Science 255, 1134 (1992), T. Zhu et al., ibid. 261, 1179 (1993); L. Q. Zhang et al., J. Virol. 67, 3345 (1993); N Ahmed, B. M. Baroudy, R C. Baker, C. Drappy, ibid. 69, 1001 (1995); J. W. Mallors et al., Ann. Intern. Med 122, 573 (1995); E. C. Holmes, L. Q. Zang, P Simmonds, C. A Ludlam, A. J. Leigh-Brown, Proc Natl. Acad Sci. U.S A 89, 4835 (1992); B. T. M. Korber et al., AIDS Res Hum. Retroviruses 8, 1461 (1992); C L Kuiken et al., J. Virol. 66, 4622 (1992); T. F. W. Woffs, G. Zwart, M. Bakker, J. Goudsmit, Virology 189, 103 (1992).
13. S M. Wolinsky et al , Science 255, 1134 (1992), T. Zhu et al., ibid. 261, 1179 (1993); L. Q. Zhang et al., J. Virol. 67, 3345 (1993); N Ahmed, B. M. Baroudy, R C. Baker, C. Drappy, ibid. 69, 1001 (1995); J. W. Mallors et al., Ann. Intern. Med 122, 573 (1995); E. C. Holmes, L. Q. Zang, P Simmonds, C. A Ludlam, A. J. Leigh-Brown, Proc Natl. Acad Sci. U.S A 89, 4835 (1992); B. T. M. Korber et al., AIDS Res Hum. Retroviruses 8, 1461 (1992); C L Kuiken et al., J. Virol. 66, 4622 (1992); T. F. W. Woffs, G. Zwart, M. Bakker, J. Goudsmit, Virology 189, 103 (1992).
14. R. A. Koup et al , J. Virol. 68, 4640 (1994).
15. M. E Eyster, J. O. Ballard, M. H. Gail, J. E. Drummond, J. J. Goedert, Ann. Intern. Med. 110, 963 (1989); G. Rutherford et al., Br. Med. J. 301, 1183 (1990); H Sheppard, W Lang, M Ascher, E. Vitting hoff, W. Winklestein, AIDS 7, 1159 (1993); S. Buchbinder, M. Kate, N. Hessol, P. O'Malky, S. Holmberg, ibid 8, 393 (1994); L. K. Schrager, J. M Young, M. G. Fowler, B. J. Mathieson, S. H. Vermund, ibid., p. 895; I Kelt et al., J. Infect. Dis. 169, 1236 (1994); T. C Greenough et al., AIDS Res. Hum. Retroviruses 10, 395 (1994).
16. M. E Eyster, J. O. Ballard, M. H. Gail, J. E. Drummond, J. J. Goedert, Ann. Intern. Med. 110, 963 (1989); G. Rutherford et al., Br. Med. J. 301, 1183 (1990); H Sheppard, W Lang, M Ascher, E. Vitting hoff, W. Winklestein, AIDS 7, 1159 (1993); S. Buchbinder, M. Kate, N. Hessol, P. O'Malky, S. Holmberg, ibid 8, 393 (1994); L. K. Schrager, J. M Young, M. G. Fowler, B. J. Mathieson, S. H. Vermund, ibid., p. 895; I Kelt et al., J. Infect. Dis. 169, 1236 (1994); T. C Greenough et al., AIDS Res. Hum. Retroviruses 10, 395 (1994).
17. M. E Eyster, J. O. Ballard, M. H. Gail, J. E. Drummond, J. J. Goedert, Ann. Intern. Med. 110, 963 (1989); G. Rutherford et al., Br. Med. J. 301, 1183 (1990); H Sheppard, W Lang, M Ascher, E. Vitting hoff, W. Winklestein, AIDS 7, 1159 (1993); S. Buchbinder, M. Kate, N. Hessol, P. O'Malky, S. Holmberg, ibid 8, 393 (1994); L. K. Schrager, J. M Young, M. G. Fowler, B. J. Mathieson, S. H. Vermund, ibid., p. 895; I Kelt et al., J. Infect. Dis. 169, 1236 (1994); T. C Greenough et al., AIDS Res. Hum. Retroviruses 10, 395 (1994).
18. M. E Eyster, J. O. Ballard, M. H. Gail, J. E. Drummond, J. J. Goedert, Ann. Intern. Med. 110, 963 (1989); G. Rutherford et al., Br. Med. J. 301, 1183 (1990); H Sheppard, W Lang, M Ascher, E. Vitting hoff, W. Winklestein, AIDS 7, 1159 (1993); S. Buchbinder, M. Kate, N. Hessol, P. O'Malky, S. Holmberg, ibid 8, 393 (1994); L. K. Schrager, J. M Young, M. G. Fowler, B. J. Mathieson, S. H. Vermund, ibid., p. 895; I Kelt et al., J. Infect. Dis. 169, 1236 (1994); T. C Greenough et al., AIDS Res. Hum. Retroviruses 10, 395 (1994).
19. M. E Eyster, J. O. Ballard, M. H. Gail, J. E. Drummond, J. J. Goedert, Ann. Intern. Med. 110, 963 (1989); G. Rutherford et al., Br. Med. J. 301, 1183 (1990); H Sheppard, W Lang, M Ascher, E. Vitting hoff, W. Winklestein, AIDS 7, 1159 (1993); S. Buchbinder, M. Kate, N. Hessol, P. O'Malky, S. Holmberg, ibid 8, 393 (1994); L. K. Schrager, J. M Young, M. G. Fowler, B. J. Mathieson, S. H. Vermund, ibid., p. 895; I Kelt et al., J. Infect. Dis. 169, 1236 (1994); T. C Greenough et al., AIDS Res. Hum. Retroviruses 10, 395 (1994).
20. M. E Eyster, J. O. Ballard, M. H. Gail, J. E. Drummond, J. J. Goedert, Ann. Intern. Med. 110, 963 (1989); G. Rutherford et al., Br. Med. J. 301, 1183 (1990); H Sheppard, W Lang, M Ascher, E. Vitting hoff, W. Winklestein, AIDS 7, 1159 (1993); S. Buchbinder, M. Kate, N. Hessol, P. O'Malky, S. Holmberg, ibid 8, 393 (1994); L. K. Schrager, J. M Young, M. G. Fowler, B. J. Mathieson, S. H. Vermund, ibid., p. 895; I Kelt et al., J. Infect. Dis. 169, 1236 (1994); T. C Greenough et al., AIDS Res. Hum. Retroviruses 10, 395 (1994).
21. M. E Eyster, J. O. Ballard, M. H. Gail, J. E. Drummond, J. J. Goedert, Ann. Intern. Med. 110, 963 (1989); G. Rutherford et al., Br. Med. J. 301, 1183 (1990); H Sheppard, W Lang, M Ascher, E. Vitting hoff, W. Winklestein, AIDS 7, 1159 (1993); S. Buchbinder, M. Kate, N. Hessol, P. O'Malky, S. Holmberg, ibid 8, 393 (1994); L. K. Schrager, J. M Young, M. G. Fowler, B. J. Mathieson, S. H. Vermund, ibid., p. 895; I Kelt et al., J. Infect. Dis. 169, 1236 (1994); T. C Greenough et al., AIDS Res. Hum. Retroviruses 10, 395 (1994).
22. B. Asjo et al., Lancet ii, 660 (1986); M. R. Tersmette et al., J. Virol. 62, 2026 (1988); M. R Tersmette et al., ibid 63, 2118 (1989); H. Schuitemaker et al , ibid 66, 1354 (1992): R. I. Connor, H. Mohri, Y. Cao, D D Ho, ibid. 67, 1772 (1993); C. Nielsen, C. Pederson, J. D. Lundgren, J. Gerstoft, AIDS 7, 1035 (1993); M. Koot et al., Ann. Intern. Med. 118, 742 (1993); R. Connor and D. D. Ho, J. Virol 68, 4400 (1994); D Richman and S. Bozzette, J. Infect. Dis. 169, 968 (1994)
23. B. Asjo et al., Lancet ii, 660 (1986); M. R. Tersmette et al., J. Virol. 62, 2026 (1988); M. R Tersmette et al., ibid 63, 2118 (1989); H. Schuitemaker et al , ibid 66, 1354 (1992): R. I. Connor, H. Mohri, Y. Cao, D D Ho, ibid. 67, 1772 (1993); C. Nielsen, C. Pederson, J. D. Lundgren, J. Gerstoft, AIDS 7, 1035 (1993); M. Koot et al., Ann. Intern. Med. 118, 742 (1993); R. Connor and D. D. Ho, J. Virol 68, 4400 (1994); D Richman and S. Bozzette, J. Infect. Dis. 169, 968 (1994)
24. B. Asjo et al., Lancet ii, 660 (1986); M. R. Tersmette et al., J. Virol. 62, 2026 (1988); M. R Tersmette et al., ibid 63, 2118 (1989); H. Schuitemaker et al , ibid 66, 1354 (1992): R. I. Connor, H. Mohri, Y. Cao, D D Ho, ibid. 67, 1772 (1993); C. Nielsen, C. Pederson, J. D. Lundgren, J. Gerstoft, AIDS 7, 1035 (1993); M. Koot et al., Ann. Intern. Med. 118, 742 (1993); R. Connor and D. D. Ho, J. Virol 68, 4400 (1994); D Richman and S. Bozzette, J. Infect. Dis. 169, 968 (1994)
25. B. Asjo et al., Lancet ii, 660 (1986); M. R. Tersmette et al., J. Virol. 62, 2026 (1988); M. R Tersmette et al., ibid 63, 2118 (1989); H. Schuitemaker et al , ibid 66, 1354 (1992): R. I. Connor, H. Mohri, Y. Cao, D D Ho, ibid. 67, 1772 (1993); C. Nielsen, C. Pederson, J. D. Lundgren, J. Gerstoft, AIDS 7, 1035 (1993); M. Koot et al., Ann. Intern. Med. 118, 742 (1993); R. Connor and D. D. Ho, J. Virol 68, 4400 (1994); D Richman and S. Bozzette, J. Infect. Dis. 169, 968 (1994)
26. B. Asjo et al., Lancet ii, 660 (1986); M. R. Tersmette et al., J. Virol. 62, 2026 (1988); M. R Tersmette et al., ibid 63, 2118 (1989); H. Schuitemaker et al , ibid 66, 1354 (1992): R. I. Connor, H. Mohri, Y. Cao, D D Ho, ibid. 67, 1772 (1993); C. Nielsen, C. Pederson, J. D. Lundgren, J. Gerstoft, AIDS 7, 1035 (1993); M. Koot et al., Ann. Intern. Med. 118, 742 (1993); R. Connor and D. D. Ho, J. Virol 68, 4400 (1994); D Richman and S. Bozzette, J. Infect. Dis. 169, 968 (1994)
27. B. Asjo et al., Lancet ii, 660 (1986); M. R. Tersmette et al., J. Virol. 62, 2026 (1988); M. R Tersmette et al., ibid 63, 2118 (1989); H. Schuitemaker et al , ibid 66, 1354 (1992): R. I. Connor, H. Mohri, Y. Cao, D D Ho, ibid. 67, 1772 (1993); C. Nielsen, C. Pederson, J. D. Lundgren, J. Gerstoft, AIDS 7, 1035 (1993); M. Koot et al., Ann. Intern. Med. 118, 742 (1993); R. Connor and D. D. Ho, J. Virol 68, 4400 (1994); D Richman and S. Bozzette, J. Infect. Dis. 169, 968 (1994)
28. B. Asjo et al., Lancet ii, 660 (1986); M. R. Tersmette et al., J. Virol. 62, 2026 (1988); M. R Tersmette et al., ibid 63, 2118 (1989); H. Schuitemaker et al , ibid 66, 1354 (1992): R. I. Connor, H. Mohri, Y. Cao, D D Ho, ibid. 67, 1772 (1993); C. Nielsen, C. Pederson, J. D. Lundgren, J. Gerstoft, AIDS 7, 1035 (1993); M. Koot et al., Ann. Intern. Med. 118, 742 (1993); R. Connor and D. D. Ho, J. Virol 68, 4400 (1994); D Richman and S. Bozzette, J. Infect. Dis. 169, 968 (1994)
29. B. Asjo et al., Lancet ii, 660 (1986); M. R. Tersmette et al., J. Virol. 62, 2026 (1988); M. R Tersmette et al., ibid 63, 2118 (1989); H. Schuitemaker et al , ibid 66, 1354 (1992): R. I. Connor, H. Mohri, Y. Cao, D D Ho, ibid. 67, 1772 (1993); C. Nielsen, C. Pederson, J. D. Lundgren, J. Gerstoft, AIDS 7, 1035 (1993); M. Koot et al., Ann. Intern. Med. 118, 742 (1993); R. Connor and D. D. Ho, J. Virol 68, 4400 (1994); D Richman and S. Bozzette, J. Infect. Dis. 169, 968 (1994)
30. B. Asjo et al., Lancet ii, 660 (1986); M. R. Tersmette et al., J. Virol. 62, 2026 (1988); M. R Tersmette et al., ibid 63, 2118 (1989); H. Schuitemaker et al , ibid 66, 1354 (1992): R. I. Connor, H. Mohri, Y. Cao, D D Ho, ibid. 67, 1772 (1993); C. Nielsen, C. Pederson, J. D. Lundgren, J. Gerstoft, AIDS 7, 1035 (1993); M. Koot et al., Ann. Intern. Med. 118, 742 (1993); R. Connor and D. D. Ho, J. Virol 68, 4400 (1994); D Richman and S. Bozzette, J. Infect. Dis. 169, 968 (1994)
31. J. Learmont et al., Lancet 341, 113 (1993); R. C. Desrosiers, AIDS Res. Hum. Retroviruses 8, 411 (1992); N. L. Michaels et al., J. Virol. 69, 1868 (1995); N. L. Michaels et al., ibid., p. 6758, F. Kirchhoff, T. C. Greenough, D. B. Brettler, J. L. Sullivan, R. C. Desrosiers, N. Engl. J Med. 332, 228 (1995); A K M. Iversen et al., J. Virol. 69, 5743 (1995).
32. J. Learmont et al., Lancet 341, 113 (1993); R. C. Desrosiers, AIDS Res. Hum. Retroviruses 8, 411 (1992); N. L. Michaels et al., J. Virol. 69, 1868 (1995); N. L. Michaels et al., ibid., p. 6758, F. Kirchhoff, T. C. Greenough, D. B. Brettler, J. L. Sullivan, R. C. Desrosiers, N. Engl. J Med. 332, 228 (1995); A K M. Iversen et al., J. Virol. 69, 5743 (1995).
33. J. Learmont et al., Lancet 341, 113 (1993); R. C. Desrosiers, AIDS Res. Hum. Retroviruses 8, 411 (1992); N. L. Michaels et al., J. Virol. 69, 1868 (1995); N. L. Michaels et al., ibid., p. 6758, F. Kirchhoff, T. C. Greenough, D. B. Brettler, J. L. Sullivan, R. C. Desrosiers, N. Engl. J Med. 332, 228 (1995); A K M. Iversen et al., J. Virol. 69, 5743 (1995).
34. J. Learmont et al., Lancet 341, 113 (1993); R. C. Desrosiers, AIDS Res. Hum. Retroviruses 8, 411 (1992); N. L. Michaels et al., J. Virol. 69, 1868 (1995); N. L. Michaels et al., ibid., p. 6758, F. Kirchhoff, T. C. Greenough, D. B. Brettler, J. L. Sullivan, R. C. Desrosiers, N. Engl. J Med. 332, 228 (1995); A K M. Iversen et al., J. Virol. 69, 5743 (1995).
35. J. Learmont et al., Lancet 341, 113 (1993); R. C. Desrosiers, AIDS Res. Hum. Retroviruses 8, 411 (1992); N. L. Michaels et al., J. Virol. 69, 1868 (1995); N. L. Michaels et al., ibid., p. 6758, F. Kirchhoff, T. C. Greenough, D. B. Brettler, J. L. Sullivan, R. C. Desrosiers, N. Engl. J Med. 332, 228 (1995); A K M. Iversen et al., J. Virol. 69, 5743 (1995).
36. J. Learmont et al., Lancet 341, 113 (1993); R. C. Desrosiers, AIDS Res. Hum. Retroviruses 8, 411 (1992); N. L. Michaels et al., J. Virol. 69, 1868 (1995); N. L. Michaels et al., ibid., p. 6758, F. Kirchhoff, T. C. Greenough, D. B. Brettler, J. L. Sullivan, R. C. Desrosiers, N. Engl. J Med. 332, 228 (1995); A K M. Iversen et al., J. Virol. 69, 5743 (1995).
37. Y. Cao, L. Qin, L. Zhang, J T. Safrit, D. D. Ho, N. Engl. J. Med 332, 201 (1995)
38. M. F. Furtado, L Kingsley, S M. Wolinsky, J Virol. 69, 2092 (1994).
39. R. M. Zinkernagel and H. Hengartner, Immunol. Today 15, 262 (1994); R Cheymier et al., Cell 78, 373 (1994), S. Wain-Hobson, Nature 373, 102 (1995)
40. R. M. Zinkernagel and H. Hengartner, Immunol. Today 15, 262 (1994); R Cheymier et al., Cell 78, 373 (1994), S. Wain-Hobson, Nature 373, 102 (1995)
41. R. M. Zinkernagel and H. Hengartner, Immunol. Today 15, 262 (1994); R Cheymier et al., Cell 78, 373 (1994), S. Wain-Hobson, Nature 373, 102 (1995)
42. M. Nowak et al., Science 254, 963 (1991), M. Nowak and A. J. McMichael, Sci Am. 273, 58 (August 1995).
43. M. Nowak et al., Science 254, 963 (1991), M. Nowak and A. J. McMichael, Sci Am. 273, 58 (August 1995).
44. The positions ot the oligonucleotide primers are numbered according to the HXB2 isolate in the Human Retroviruses and AIDS Database (39) KK1-KK3 [nucleotides (nt) 6094 to 6119, 5′-TAATCAG(T/C)TTATGGGATCAAAGCCT-3′, and nt 7332 to 7357. 5′-GTCCTTCCTGCTGCTCCCAAGAACC-3′] and KK2 Eco RIKK4 Xba I [nt 6122 to 6147, 5′-GAATTCCCATGTGTAAAATTAACCCCACTCT-3′; and nt 7282 to 7307, 5′-TCTAGATGCTCTTTTTTCTCT(C/T)T(G/C)CACCACT-3′] were the outer and inner sets of amplification primers, respectively. The input DNA molecules were quantified as described (8). PCR was performed as described [B T. M. Korber et al., J Virol. 68, 7467 (1994) ] with a Perkin-Elmer/Cetus 9600 automated thermal cycler programmed for 32 cycles at 98°C for 10 s, 50°C for 15 s, and 72°C for 2 min with a final extension at 72°C for 10 min. A 5-μl sample was reamplified in a 100-μl reaction mix containing 0.2 μM of each of the inner primer pair by means of the same cycle profile as above. HIV-1-negative cell DNA and reagent controls were run in parallel [S Kwok and R Higuchi, Nature 339, 237 (1989)]. PCR-product DNA was asymmetrically inserted into pGEM3zf(-) (Promega) as described (8). One microgram of the double-stranded DNA template was sequenced in both forward (M13-21 universal and KK40 nt 6953 to 6972, 5′-ACAGTACAATGTACACATGG-3′) and reverse [M13 reverse and KK8 nt 6892 to 6917, 5′-AATTTCCCTC(C/T)ACAATTAAAACTGT-3′] directions with the use of dideoxynucleotide triphosphates (Dye-Deoxy terminators) and analyzed with a 373A sequencing system (Applied BioSystems) as described (8).
45. The positions ot the oligonucleotide primers are numbered according to the HXB2 isolate in the Human Retroviruses and AIDS Database (39) KK1-KK3 [nucleotides (nt) 6094 to 6119, 5′-TAATCAG(T/C)TTATGGGATCAAAGCCT-3′, and nt 7332 to 7357. 5′-GTCCTTCCTGCTGCTCCCAAGAACC-3′] and KK2 Eco RIKK4 Xba I [nt 6122 to 6147, 5′-GAATTCCCATGTGTAAAATTAACCCCACTCT-3′; and nt 7282 to 7307, 5′-TCTAGATGCTCTTTTTTCTCT(C/T)T(G/C)CACCACT-3′] were the outer and inner sets of amplification primers, respectively. The input DNA molecules were quantified as described (8). PCR was performed as described [B T. M. Korber et al., J Virol. 68, 7467 (1994) ] with a Perkin-Elmer/Cetus 9600 automated thermal cycler programmed for 32 cycles at 98°C for 10 s, 50°C for 15 s, and 72°C for 2 min with a final extension at 72°C for 10 min. A 5-μl sample was reamplified in a 100-μl reaction mix containing 0.2 μM of each of the inner primer pair by means of the same cycle profile as above. HIV-1-negative cell DNA and reagent controls were run in parallel [S Kwok and R Higuchi, Nature 339, 237 (1989)]. PCR-product DNA was asymmetrically inserted into pGEM3zf(-) (Promega) as described (8). One microgram of the double-stranded DNA template was sequenced in both forward (M13-21 universal and KK40 nt 6953 to 6972, 5′-ACAGTACAATGTACACATGG-3′) and reverse [M13 reverse and KK8 nt 6892 to 6917, 5′-AATTTCCCTC(C/T)ACAATTAAAACTGT-3′] directions with the use of dideoxynucleotide triphosphates (Dye-Deoxy terminators) and analyzed with a 373A sequencing system (Applied BioSystems) as described (8).
46. S. M. Wolinsky et al., data not shown.
47. The multiple aligned sequence editor (MASE) program [D Faulkner and J Jurka, Trends Biochem Sci 13, 321 (1988)] was used for the sequence alignments. For phylogenetic analysis, positions where gaps were inserted to maintain the alignment were discounted, leaving 590 positions in the 292 taxa. All sequences from this study were included in a single neighbor-joining tree construction. The phylogenetic tree was constructed with the neighbor program in PHYLIP [ J. Felsenstein, Claudistics 5, 164 (1989)] based on a Kimura two-parameter distance matrix with a ratio of transitions to transversions of 1.3. All of the within-subject sequence sets clustered together, indicating that there was no cross-contamination of samples. Additionally, representative viral sequences from each subject were compared to the viral sequences deposited in Gen-Bank with BLAST [S. F. Altschul, W. Gish, W. Miller, E. W. Myer, D. J. Lipman, J Mol. Biol 215, 403 (1990 )]. No nucleotide sequences with greater than 91% similarity were observed, indicating that contamination with a preexisting viral isolate was unlikely [B. T. M Korber, G. Leam, J. I. Mullins, B. H Hahn, S M Wolinsky, Nature 378, 242 (1995)].
48. The multiple aligned sequence editor (MASE) program [D Faulkner and J Jurka, Trends Biochem Sci 13, 321 (1988)] was used for the sequence alignments. For phylogenetic analysis, positions where gaps were inserted to maintain the alignment were discounted, leaving 590 positions in the 292 taxa. All sequences from this study were included in a single neighbor-joining tree construction. The phylogenetic tree was constructed with the neighbor program in PHYLIP [ J. Felsenstein, Claudistics 5, 164 (1989)] based on a Kimura two-parameter distance matrix with a ratio of transitions to transversions of 1.3. All of the within-subject sequence sets clustered together, indicating that there was no cross-contamination of samples. Additionally, representative viral sequences from each subject were compared to the viral sequences deposited in Gen-Bank with BLAST [S. F. Altschul, W. Gish, W. Miller, E. W. Myer, D. J. Lipman, J Mol. Biol 215, 403 (1990 )]. No nucleotide sequences with greater than 91% similarity were observed, indicating that contamination with a preexisting viral isolate was unlikely [B. T. M Korber, G. Leam, J. I. Mullins, B. H Hahn, S M Wolinsky, Nature 378, 242 (1995)].
49. The multiple aligned sequence editor (MASE) program [D Faulkner and J Jurka, Trends Biochem Sci 13, 321 (1988)] was used for the sequence alignments. For phylogenetic analysis, positions where gaps were inserted to maintain the alignment were discounted, leaving 590 positions in the 292 taxa. All sequences from this study were included in a single neighbor-joining tree construction. The phylogenetic tree was constructed with the neighbor program in PHYLIP [ J. Felsenstein, Claudistics 5, 164 (1989)] based on a Kimura two-parameter distance matrix with a ratio of transitions to transversions of 1.3. All of the within-subject sequence sets clustered together, indicating that there was no cross-contamination of samples. Additionally, representative viral sequences from each subject were compared to the viral sequences deposited in Gen-Bank with BLAST [S. F. Altschul, W. Gish, W. Miller, E. W. Myer, D. J. Lipman, J Mol. Biol 215, 403 (1990 )]. No nucleotide sequences with greater than 91% similarity were observed, indicating that contamination with a preexisting viral isolate was unlikely [B. T. M Korber, G. Leam, J. I. Mullins, B. H Hahn, S M Wolinsky, Nature 378, 242 (1995)].
50. The multiple aligned sequence editor (MASE) program [D Faulkner and J Jurka, Trends Biochem Sci 13, 321 (1988)] was used for the sequence alignments. For phylogenetic analysis, positions where gaps were inserted to maintain the alignment were discounted, leaving 590 positions in the 292 taxa. All sequences from this study were included in a single neighbor-joining tree construction. The phylogenetic tree was constructed with the neighbor program in PHYLIP [ J. Felsenstein, Claudistics 5, 164 (1989)] based on a Kimura two-parameter distance matrix with a ratio of transitions to transversions of 1.3. All of the within-subject sequence sets clustered together, indicating that there was no cross-contamination of samples. Additionally, representative viral sequences from each subject were compared to the viral sequences deposited in Gen-Bank with BLAST [S. F. Altschul, W. Gish, W. Miller, E. W. Myer, D. J. Lipman, J Mol. Biol 215, 403 (1990 )]. No nucleotide sequences with greater than 91% similarity were observed, indicating that contamination with a preexisting viral isolate was unlikely [B. T. M Korber, G. Leam, J. I. Mullins, B. H Hahn, S M Wolinsky, Nature 378, 242 (1995)].
51. The median branch lengths from each subject's ancestral node to all taxa from a given time point were calculated by means of a Kimura two-parameter distance matrix to create a neighbor-joining tree For this analysis, we used the two time points closest to the last sampling time point available for P1 (month 26) and P2 (month 35) before death. The median branch length to an ancestral node and the interquartile range was as follows: P1.26,0.013 (0.013 to 0.018), P2.27, 0.012 (0.009 to 0.015); P2.35, 0.010 (0009 to 0.010); P325, 0.022 (0.018 to 0.024); P3.49, 0.034 (0.033 to 0.034); P4.25, 0.009 (0.006 to 0 011); P4.37, 0.026 (0.021 to 0.035), P5.28, 0.018 (0.013 to 0.021); P5.34, 0.019 (0.015 to 0.027); P6.29, 0.014 (0 012 to 0.016); and P6.39, 0.007 (0.004 to 0.009). There is a trend of less divergence in P1 and P2, with median distances of one and a half- to threefold higher in P3, P4, and P6 at roughly comparable time points Because P5 had a limited input copy number, it is not possible to ascertain whether the low distance values for P5.29 and P5.39 are exceptions to the trend or sampling artifacts.
52. E. L. Delwart, H W. Sheppard, B O. Walker, J. Goudsmit, J. I. Mullins, J. Virol. 68, 6672 (1994).
53. The average numbers of synonymous substitutions per potential synonymous site and nonsynonymous substitutions per potential nonsynonymous site relative to the original consensus sequence were calculated [M. Nei and T. Gojobori, Mol. Biol. Evol. 2, 418 (1986)] for each time point for each of the six study subjects. The consensus sequence from the first sampled time point was used as a reference sequence as the best estimate of the viral form at primary infection. The extrapolated best-fit linear slopes were calculated to estimate the rate of substitution and presented as the percent substitution of each type per annum
54. For P2, the negative rate of synonymous substitutions calculated per year (-0.2% per year) was due to the low number of synonymous substitutions per synonymous site overall and the relatively greater number of synonymous substitutions in viral sequences from an early time point relative to the consensus sequence than that observed for subsequent time points.
55. S. M. Wolinsky, M. Daniels, M H. Furtado, J L. Bingham, B T. M. Korber, in Neuvieme Colloque Des Cent Gent Gardes, M. Girard and B. Dodet, Eds. (La Fondation Marcel Mérieux, Marnes-La-Coquette, France, 1994), p 95; J Mullins et al., ibid., p. 77; V. V. Lukashov, C. L. Kuiken, J. Goudsmit, J Virol. 69, 6911 (1995).
56. S. M. Wolinsky, M. Daniels, M H. Furtado, J L. Bingham, B T. M. Korber, in Neuvieme Colloque Des Cent Gent Gardes, M. Girard and B. Dodet, Eds. (La Fondation Marcel Mérieux, Marnes-La-Coquette, France, 1994), p 95; J Mullins et al., ibid., p. 77; V. V. Lukashov, C. L. Kuiken, J. Goudsmit, J Virol. 69, 6911 (1995).
57. S. M. Wolinsky, M. Daniels, M H. Furtado, J L. Bingham, B T. M. Korber, in Neuvieme Colloque Des Cent Gent Gardes, M. Girard and B. Dodet, Eds. (La Fondation Marcel Mérieux, Marnes-La-Coquette, France, 1994), p 95; J Mullins et al., ibid., p. 77; V. V. Lukashov, C. L. Kuiken, J. Goudsmit, J Virol. 69, 6911 (1995).
58. Pairwise short tandem repeat (STR)-based [S. Henikoff, New Biol. 3, 1148 (1991)] similarity scores were calculated and used as a basis for the phenograms For a set of sequences representing a diverse panel of peptides used for a peptide-based enzyme-linked immunosorbemassay [A. Pau et al., AIDS Res Hum. Retroviruses 11, 1369 (1994)], clusters generated by means of phenograms were highly correlated with the serological typing results (B. T. M. Korber, unpublished results).
59. Pairwise short tandem repeat (STR)-based [S. Henikoff, New Biol. 3, 1148 (1991)] similarity scores were calculated and used as a basis for the phenograms For a set of sequences representing a diverse panel of peptides used for a peptide-based enzyme-linked immunosorbemassay [A. Pau et al., AIDS Res Hum. Retroviruses 11, 1369 (1994)], clusters generated by means of phenograms were highly correlated with the serological typing results (B. T. M. Korber, unpublished results).
60. Pairwise short tandem repeat (STR)-based [S. Henikoff, New Biol. 3, 1148 (1991)] similarity scores were calculated and used as a basis for the phenograms For a set of sequences representing a diverse panel of peptides used for a peptide-based enzyme-linked immunosorbemassay [A. Pau et al., AIDS Res Hum. Retroviruses 11, 1369 (1994)], clusters generated by means of phenograms were highly correlated with the serological typing results (B. T. M. Korber, unpublished results).
61. B. T. M. Korber, K MacInnes, R. F. Smith, G. Myers, J. Virol. 68, 6730 (1994).
62. 1. This measure, also known as the Shannon entropy, is related to the Simpson index that has been used previously to quantify viral sequence variability within time points (10), as both are specific forms of Renyi entropies [A Renyi, Probability Theory (North-Holland, Amsterdam, 1970); P Grassberger, Phys Lett. A97, 227 (1983)]. These analyses correlated with the within-time point amino acid Hamming distances, after gap-stripping.
63. 1. This measure, also known as the Shannon entropy, is related to the Simpson index that has been used previously to quantify viral sequence variability within time points (10), as both are specific forms of Renyi entropies [A Renyi, Probability Theory (North-Holland, Amsterdam, 1970); P Grassberger, Phys Lett. A97, 227 (1983)]. These analyses correlated with the within-time point amino acid Hamming distances, after gap-stripping.
64. The association of low genetic diversity with a rapid rate of progression to AIDS has been replicated and further substantiated by the results from two natural history cohort studies of HIV-1-infected men based on the heteroduplex mobility assay (F Delwart et al., in preparation, S. Wolinsky, unpublished results) and by the results of a natural history cohort study of children with perinatal HIV-1 infection ( S Ganeshan et al., in preparation).
65. The association of low genetic diversity with a rapid rate of progression to AIDS has been replicated and further substantiated by the results from two natural history cohort studies of HIV-1-infected men based on the heteroduplex mobility assay (F Delwart et al., in preparation, S. Wolinsky, unpublished results) and by the results of a natural history cohort study of children with perinatal HIV-1 infection ( S Ganeshan et al., in preparation).
66. The association of low genetic diversity with a rapid rate of progression to AIDS has been replicated and further substantiated by the results from two natural history cohort studies of HIV-1-infected men based on the heteroduplex mobility assay (F Delwart et al., in preparation, S. Wolinsky, unpublished results) and by the results of a natural history cohort study of children with perinatal HIV-1 infection ( S Ganeshan et al., in preparation).
67. Neutralization studies were conducted by testing an early and a late isolate against a panel of early sera and late sera from each of the six subjects. Consistent with the observation that a neutralizing antibody response develops gradually [J. P. Moore, Y. Cao, D. D. Ho, R A. Koup, J. Virol. 68, 5142 (1994)], most of the sera obtained from these participants at an earlier time point had little or no neutralizing activity. The geometric mean liter of the reciprocal dilution of early sera needed to neutralize 90% of an autotogous or heterologous virus inoculum (no neutralization was arbitranly set at 0.01) for all six subjects ranged from 0.03 to 0 06. The geometric mean titers of the reciprocal dilution of late sera needed to neutralize 90% of a virus inoculum were 0.03 for P1, 0 2 for P2, 5 6 for P3, 7.9 for P4, 1.8 for P5, and 0.2 for P6 Therefore, we did not observe a clear association between neutralization capability and the rate of progression to disease Additionally, the viruses isolated early and late from P1 and the virus isolated late from P2 were the only viruses neutralized by early serum and were generally the most easily neutralized viruses isolated. Mean reciprocal titers of 28.5 and 22.6 were observed for early and late viruses isolated from P1, respectively, and 5.3 for a late virus isolated from P2 The viruses isolated from the blood obtained from the other four subjects had mean reciprocal titers ranging from 0.01 to 3.7. Thus, the propagated viruses from rapid progressors P1 and P2 may be intrinsically easier to neutralize.
68. D. P. W. Burns, C. Collignon, R. C. Desrosiers, J Virol. 67, 4104 (1993)
69. A J. McMichael and B. D. Walker, AIDS 8, S155 (1994); J. T. Safrit, A. Y. Lee, C. A. Andrews, R. A. Koup, J. Immunol 153, 3822 (1994); R P. Johnson, A Trocha, T. M. Buchanan, B D. Walker, J. Virol 67, 438 (1993).
70. A J. McMichael and B. D. Walker, AIDS 8, S155 (1994); J. T. Safrit, A. Y. Lee, C. A. Andrews, R. A. Koup, J. Immunol 153, 3822 (1994); R P. Johnson, A Trocha, T. M. Buchanan, B D. Walker, J. Virol 67, 438 (1993).
71. A J. McMichael and B. D. Walker, AIDS 8, S155 (1994); J. T. Safrit, A. Y. Lee, C. A. Andrews, R. A. Koup, J. Immunol 153, 3822 (1994); R P. Johnson, A Trocha, T. M. Buchanan, B D. Walker, J. Virol 67, 438 (1993).
72. I. Couillin et al., J. Exp. Med 180, 1129 (1994); M. A. Nowak et al , Nature 375, 534 (1995); B. Autran et al., in Dixième Colloque Des Ceut Gardes, J.-P. Levy and M. Girard, Eds. (La Fondation Marcel Méneux, Marnes-La-Coquette, France, 1996), p 118.
73. I. Couillin et al., J. Exp. Med 180, 1129 (1994); M. A. Nowak et al , Nature 375, 534 (1995); B. Autran et al., in Dixième Colloque Des Ceut Gardes, J.-P. Levy and M. Girard, Eds. (La Fondation Marcel Méneux, Marnes-La-Coquette, France, 1996), p 118.
74. I. Couillin et al., J. Exp. Med 180, 1129 (1994); M. A. Nowak et al , Nature 375, 534 (1995); B. Autran et al., in Dixième Colloque Des Ceut Gardes, J.-P. Levy and M. Girard, Eds. (La Fondation Marcel Méneux, Marnes-La-Coquette, France, 1996), p 118.
75. To evaluate the biological phenotype of the viruses isolated from each subject, we tested four to six separate first passage virus culture stocks covering the course of infection for their capacity to replicate in primary cultures of normal donor peripheral blood mononuclear cells and monocyte-derived macrophages and for their syncytium-inducing properties in cultures of the established MT-2-transformed T cell line. The isolated viruses were expanded once in normal donor peripheral blood mononuclear cells, and titers were determined for infectivity as described [R I. Connor, H. Mohn, Y. Cao, D. D. Ho, J. Virol. 67, 1772 (1993)].
76. R. A. M. Fouchier et al., J. Virol. 66, 3183 (1992); F. de Wolf et al., AIDS Res. Hum. Retroviruses 10, 1387 (1994).
77. R. A. M. Fouchier et al., J. Virol. 66, 3183 (1992); F. de Wolf et al., AIDS Res. Hum. Retroviruses 10, 1387 (1994).
78. M. L. Bonyhadi et al., Nature 363, 728 (1993).
79. R. A. Koup et al., in preparation.
80. J. V. Giorgi et al., J. Acquired Immune Defic. Syndr. 5, 904 (1993); F. Miedema et al., Immunol Rev. 140, 35 (1994); G. Pantaleo et al , ibid., p. 105; C. Rinaldo et al., J. Virol. 69, 5838 (1995); M. R. Klein et al., J. Exp. Med. 181, 1365 (1995).
81. J. V. Giorgi et al., J. Acquired Immune Defic. Syndr. 5, 904 (1993); F. Miedema et al., Immunol Rev. 140, 35 (1994); G. Pantaleo et al , ibid., p. 105; C. Rinaldo et al., J. Virol. 69, 5838 (1995); M. R. Klein et al., J. Exp. Med. 181, 1365 (1995).
82. J. V. Giorgi et al., J. Acquired Immune Defic. Syndr. 5, 904 (1993); F. Miedema et al., Immunol Rev. 140, 35 (1994); G. Pantaleo et al , ibid., p. 105; C. Rinaldo et al., J. Virol. 69, 5838 (1995); M. R. Klein et al., J. Exp. Med. 181, 1365 (1995).
83. J. V. Giorgi et al., J. Acquired Immune Defic. Syndr. 5, 904 (1993); F. Miedema et al., Immunol Rev. 140, 35 (1994); G. Pantaleo et al , ibid., p. 105; C. Rinaldo et al., J. Virol. 69, 5838 (1995); M. R. Klein et al., J. Exp. Med. 181, 1365 (1995).
84. J. V. Giorgi et al., J. Acquired Immune Defic. Syndr. 5, 904 (1993); F. Miedema et al., Immunol Rev. 140, 35 (1994); G. Pantaleo et al , ibid., p. 105; C. Rinaldo et al., J. Virol. 69, 5838 (1995); M. R. Klein et al., J. Exp. Med. 181, 1365 (1995).
85. M. Eigen, Cold Spring Harbor Symp. Quant. Biol. 52, 307 (1987), J. J. Holland, J. C LaTorre, D. A. Steinhauer, Curr. Top. Microbiol Immunol. 176, 1 (1992).
86. M. Eigen, Cold Spring Harbor Symp. Quant. Biol. 52, 307 (1987), J. J. Holland, J. C LaTorre, D. A. Steinhauer, Curr. Top. Microbiol Immunol. 176, 1 (1992).
87. M. Eigen and C. K. Biebricker, in RNA Genetics, E. Domingo et al., Eds. (CRC, Boca Raton, FL, 1988), vol 3, p. 211-245.
88. D. A. Steinhauer, J. C. De La Torre, J. J. Holland, J. Virol 63, 2063 (1989); D. A. Steinhauer, J. C. De La Torre, E. Meier, J J. Holland, ibid., p. 2072; J. C. De La Torre, E. Wimmer, J. J. Holland, ibid 64, 664 (1990).
89. D. A. Steinhauer, J. C. De La Torre, J. J. Holland, J. Virol 63, 2063 (1989); D. A. Steinhauer, J. C. De La Torre, E. Meier, J J. Holland, ibid., p. 2072; J. C. De La Torre, E. Wimmer, J. J. Holland, ibid 64, 664 (1990).
90. D. A. Steinhauer, J. C. De La Torre, J. J. Holland, J. Virol 63, 2063 (1989); D. A. Steinhauer, J. C. De La Torre, E. Meier, J J. Holland, ibid., p. 2072; J. C. De La Torre, E. Wimmer, J. J. Holland, ibid 64, 664 (1990).
91. S Wright, in Evolution and the Genetics of Populations (Univ of Chicago Press, 1977), vols. 1 to 4; Evolution 36, 427 (1982).
92. S Wright, in Evolution and the Genetics of Populations (Univ of Chicago Press, 1977), vols. 1 to 4; Evolution 36, 427 (1982).
93. R Lande, Proc Natl. Acad. Sci. U S.A. 82, 7641 (1985); C. M. Neuman, J. E. Cohn, C. Kipnis, Nature 315, 400 (1985).
94. R Lande, Proc Natl. Acad. Sci. U S.A. 82, 7641 (1985); C. M. Neuman, J. E. Cohn, C. Kipnis, Nature 315, 400 (1985).
95. J. M. Coffin, Science 267, 483 (1995).
96. A. M. Munoz et al , J. Acquired Immune Defic Syndr. 8, 496 (1995).
97. G. Myers et al., Eds., Human Retroviruses and AIDS Database (Theoretical Biology, Los Alamos National Laboratory, Los Alamos, NM, 1994)
98. J. Felsenstein, PHYLIP (phylogeny interference package) version 3.5c; Department of Genetics, University of Washington, Seattle, WA, 1993.
99. D. Swoffend, thesis, University of Illinois, Urbana-Champaign, IL (1988)
100. S. Henikoff, New Biol. 3, 1148 (1991).
101. Supported by the National Institute of Allergy and Infectious Diseases under awards AI-32535, AI-45218, AI-35522, and R-1439-94 and by a gift from an anonymous foundation. We thank D. Panicali and G. Mazzara for the vaccinia constructs; J. Bingham, D McDonald, S. K Macomber, and A Ploss for technical assistance; and L. Chow, J. Moore, J. Theiler, A Haase, J. Phair, G. Myers, and J. Coffin for advice and discussion. Sequences have been submitted to Gen-Bank under accession numbers U35894 to U36185, and alignments are available from the Human Retroviruses and AIDS Database.