B-Cell Sites in the HIV Glycoproteins

  • Ewa Björling
  • Erling Norrby


HIV, like other lentiviruses, has the capacity to direct the synthesis of a large number of different proteins. Some of these proteins participate in the formation of virus particles, whereas other proteins of a nonstructural nature appear in infected cells and may be released by secretion or in connection with a possible death of such cells. Each of these different proteins has a varying number of immunogenic sites, which may elicit humoral as well as cell-mediated responses. An acute infection with HIV as a consequence can lead to the mobilization of a large spectrum of immune responses. It is a daunting task to define the dynamics and specificities of these reactions. A considerable amount of information has already accumulated in this field, but more knowledge is needed to provide a comprehensive understanding of the complete relationship. There are three major contexts in which knowledge of HIV immunobiology is applicable.


Human Immunodeficiency Virus Acquire Immune Deficiency Syndrome Human Monoclonal Antibody Envelope Glycoprotein Acquire Immune Deficiency Syndrome Patient 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Abacioglu, Y. H., Fouts, T. R., Laman, J. D., Claassen, E., Pincus, S. H., Moore, J. P., Roby, C. A., and Kamin-Lewis, R., 1994, Epitope mapping and topology of baculovirus-expressed HIV-1 gp160 determined with panel of murine monoclonal antibodies, AIDS Res. Hum. Retrovir. 10(4):371–381.PubMedCrossRefGoogle Scholar
  2. Åkerblom, L., Hinkula, J., Broliden, P.-A., Makitalo, B., Fridbreger T., and Rosen, J., 1990, Neutralizing cross-reactive and non-neutralizing monoclonal antibodies to HIV-1 gp120, AIDS 4:953–960.PubMedCrossRefGoogle Scholar
  3. Albert, J., Bredberg, U., Chiodi, F., Böttiger, B., Fenyö, E.-M., Norrby, E., and Biberfeld, G., 1987, A new human retrovirus isolate of West African origin and its relationship to HTLV-IV, LAV-II and HTLV-IIIB, AIDS Res. Hum. Retrovir. 3:3–10.PubMedCrossRefGoogle Scholar
  4. Albeit, J., Abrahamsson, B., Nagy, K., Aurelius, E., Gaines, H., Nyström, G., and Fenyö, E. M., 1990, Rapid development of isolate-specific neutralizing antibodies after primary HIV-1 infection and consequent emergence of virus variants which resist neutralization by autologous sera, AIDS 4:107–112.CrossRefGoogle Scholar
  5. Alexander, S., and Elder, J. H., 1984, Carbohydrate dramatically influences immune reactivity of antisera to viral glycoprotein antigens, Science 226:1328–1330.PubMedCrossRefGoogle Scholar
  6. Allan, J. S., Coligan, J. E., Barin, F., McLane, M. R., Sodroski, J. F., Rosen, C. A., Haseltine, W. A., Lee, T. H., and Essex, M., 1985, Major glycoprotein antigens that induce antibodies in AIDS patients are encoded by HTLV-III, Science 228:1091–1094.PubMedCrossRefGoogle Scholar
  7. Ardman, B., Kowalski, M., Bristol, J., Haseltine, W., and Sodroski, J., 1990, Effects of CD4 binding of anti-peptide sera to the fourth and fifth conserved domains of HIV-1 gp120, J. Acq. Immune Defic. Syndr. 3:206–214.Google Scholar
  8. Arendrup, M., Nielsen, C., Hansen, J. E., Pedersen, C., Mathiesen, L., and Nielsen, J. O., 1992, Autologous HIV-1 neutralizing antibodies: Emergence of neutralization-resistant escape virus and subsequent development of virus neutralizing antibodies, J. Acq. Immune Defic. Syndr. 5:303–307.Google Scholar
  9. Åsjö, B., Morfeldt-Månsson, L., Albert, J., Biberfeld, G., Karlsson, A., Lidman, K., and Fenyö, E.-M., 1986, Replicative capacity of human immunodeficiency virus from patients with varying severity of HIV infection, Lancet 2:660–662.PubMedGoogle Scholar
  10. Babas, T., Benichou, S., Guetard, D., Montagnier, L., and Bahraoui, E., 1994, Specificity of antipeptide antibodies produced against V2 and V3 regions of the external envelope of human immunodeficiency virus type 2, Mol. Immunol. 31:361–369.PubMedCrossRefGoogle Scholar
  11. Barbas, C. F., III, Björling, E., Chiodi, F., Dunlop, N., Cababa, D., Jones, T. M., Zebedee, S. L., Persson, M. A., Nara, P. L., Norrby, E., and Burton, D. R., 1992, Recombinant human Fab fragments neutralize human type 1 immunodeficiency virus in vitro, Proc. Natl. Acad. Sci. USA 89:9339–9343.PubMedCrossRefGoogle Scholar
  12. Barré-Sinoussi, F., Cherman, F. C., Rey, F., Nugeyre, M., Chamaret, S., Gruest, J., Dauguet, G., Axler-Blin, G., Brun-Vezinet, R., Rouzioux, G., Rozenbaum, W., and Montagnier, L., 1983, Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS), Science 220:868–870.PubMedCrossRefGoogle Scholar
  13. Berzofsky, J. A., 1993, Epitope selection and design of synthetic vaccines. Molecular approaches to enhancing immunogenicity and cross-reactivity of engineered vaccines, Ann. N.Y. Acad. Sci. 690:256–264.PubMedCrossRefGoogle Scholar
  14. Björling, E., Broliden, K., Bernardi, D., Utter, G., Thorstensson, R., Chiodi, F., and Norrby, E., 1991, Hyperimmune antisera against synthetic peptides representing the glycoprotein of human immunodeficiency virus type 2 can mediate neutralization and antibody-dependent cytotoxic activity, Proc. Natl. Acad. Sci. USA 88:6082–6086.PubMedCrossRefGoogle Scholar
  15. Björling, E., Scarlatti, G., von Gegerfelt, A., Albert, J., Biberfeld, G., Chiodi, F., Norrby, E., and Fenyö, E.-M., 1993, Autologous neutralizing antibodies prevail in HIV-2 but not in HIV-1 infection, Virology 193:528–530.PubMedCrossRefGoogle Scholar
  16. Björling, E., Chiodi, F., Utter, G., and Norrby, E., 1994, Two V3 associated important neutralizing domains in the envelope glycoprotein gp125 of human immunodeficiency virus type 2, J. Immunol. 152:1952–1959.PubMedGoogle Scholar
  17. Böttiger, B., Karlsson, A., Naucler, A., Andreasson, P. Å., Mendes Costa, G., and Biberfeld, G., 1989, Cross-neutralizing antibodies against HIV-1 (HTLV-IIIB and HTLV-III RF) and HIV-2 (SBL-6669 and a new isolate SBL-K135), AIDS Res. Hum. Retrovir. 5:511–519.CrossRefGoogle Scholar
  18. Böttiger, B., Karlsson, A., Andreasson, P. Å., Naucler, A., Mendes Costa, G., Norrby, E., and Biberfeld, G., 1990, Envelope cross reactivity between human immunodeficiency virus type 1 and 2 detected by different serological methods: Correlation between cross neutralization and reactivity against the main neutralizing site, J. Virol. 64:3492–3499.PubMedGoogle Scholar
  19. Breuer, J., Douglas, N. W., Goldman, N., and Daniels, R. S., 1995, Human immunodeficiency virus type 2 (HIV-2) env gene analysis: Prediction of glycoprotein epitopes important for heterotypic neutralization and evidence for three genotype clusters within the HIV-2a subtype, J. Gen. Virol 76:333–345.PubMedCrossRefGoogle Scholar
  20. Bristow, R. G., Douglas, A. R., Skehel, J. J., and Daniels, R. S., 1994, Analysis of murine antibody responses to baculovirus-expressed human immunodeficiency virus type 1 envelope glycoproteins, J. Gen. Virol. 75:2089–2095.PubMedCrossRefGoogle Scholar
  21. Broliden, P.-A., von Gegerfelt, A., Clapham, P., Rosen, J., Fenyö, E.-M., Wahren, B., and Broliden, K., 1992, Identification of human neutralization-inducing regions of the human immunodeficiency virus type 1 envelope glycoproteins, Proc. Natl. Acad. Sci. USA 89:461–465.PubMedCrossRefGoogle Scholar
  22. Burton, D. R., Pyati, J., Koduri, R., Sharp, S. J., Thornton, G. B., Parren, P. W., Sawyer, L. S., Hendry, R. M., Dunlop, N., Nara, P. L., Lamacchia, M., Garratty, E., Stiehm, E. R., Bryson, Y. J., Cao, Y., Moore, J. P., Ho, D. D., and Barbas, C. R., III, 1994, Efficient neutralization of primary isolates of HIV-1 by a recombinant human monoclonal antibody, Science 266:1024–1027.PubMedCrossRefGoogle Scholar
  23. Cavacini, L. A., Ernes, C. L., Power, J., Underdahl, J., Goldstein, R., Mayer, K., and Posner, M. R., 1993, Loss of serum antibodies to a conformational epitope of HIV-l/gp120 identified by a human monoclonal antibody is associated with disease progression, J. Acq. Immune Defic. Syndr. 6:1093–1102.Google Scholar
  24. Chanh, T., Dreesman, G., Kanda, P., Linette, G., Sparrow, J., Ho, D., and Kennedy, R., 1986, Induction of anti-HIV neutralizing antibodies by synthetic peptides, EMBO J. 11:3065–3071.Google Scholar
  25. Charbit, A., Molla, A., Ronco, J., Clement, J. M., Favier, V., Bahraoui, E. M., Montagnier, L., Leguern, A., and Hofnung, M., 1990, Immunogenicity and antigenicity of conserved peptides from the envelope of HIV-1 expressed at the surface of recombinant bacteria, AIDS 4:545–551.PubMedCrossRefGoogle Scholar
  26. Chiodi, F., von Gegerfelt, A., Albert, J., Fenyö, E.-M., Gaines, H., von Sydow, M., Biberfeld, G., Parks, E., and Norrby, E., 1987, Site directed ELISA with synthetic peptides representing the HIV transmembrane glycoprotein, J. Med. Virol. 23:1–9.PubMedCrossRefGoogle Scholar
  27. Clavel, F., Guetard, D., Brun-Vezinet, F., Chamaret, S., Rey, M. A., Santos-Ferreria, M. O., Laurent, A. G., Dauguet, C., Katlama, C., Rouzioux, C., Klatzmann, D., Champalimaud, J. L., and Montagnier, L., 1986, Isolation of a new human retrovirus from West African patients with AIDS, Science 233:343–346.PubMedCrossRefGoogle Scholar
  28. Conley, A. J., Kessler, J. A., II, Boots, L. J., Tung, J.-S., Arnold, B., Keller, P. M., Shaw, A., and Emini, E., 1994, Neutralization of divergent human immunodeficiency virus type 1 variants and primary isolates by IAM-41-2F5, an anti-gp41 human monoclonal antibody, Proc. Natl. Acad. Sci. USA 91:3348–3352.PubMedCrossRefGoogle Scholar
  29. Cordell, J., Moore, J. P., Dean, C. J., Klasse, P. J., Weiss, R. A., and McKeating, J. A., 1991, Rat monoclonal antibodies to non-overlapping epitopes of HIV-1 gp120 block CD4 binding in vitro, Virology 185:72–79.PubMedCrossRefGoogle Scholar
  30. Cordonnier, A., Montagnier, L., and Emerman, M., 1989, Single amino acid changes in HIV envelope affect viral tropism and receptor binding, Nature 340:571–574.PubMedCrossRefGoogle Scholar
  31. Dalgleish, A. G., Chanh, T. C., Kennedy, R. C., Kanda, P., Clapham, P. R., and Weiss, R. A., 1988, Neutralization of diverse HIV-1 strains by monoclonal antibodies raised against a gp41 synthetic peptide, Virology 165:209–215.PubMedCrossRefGoogle Scholar
  32. Davis, D., Stephens, D.M., Carne, C. A., and Lachmann, P. J., 1993, Antisera raised against the second variable region of the external envelope glycoprotein of human immunodeficiency virus type 1 cross-neutralize and show an increased neutralization index when they act together with antisera to the V3 neutralization epitope, J. Gen. Virol. 74:2609–2617.PubMedCrossRefGoogle Scholar
  33. De Cock, K. M., Odehouri, K., Colebunders, R. L., Adjorlolo, G., Lafontaine, M. F., Porter, A., Gnaore, E., Diaby, L., Moreau, J., Heyward, W. L., Kadio, A., Heroin, P., Kanga, J.-M., Beda, B., Niamkey, E., Achi, Y., Coulibaly, N., Attia, Y., Giordano, C., Rayfield, M., and Schochetman, G., 1990, A comparison of HIV-1 and HIV-2 infections in hospitalized patients in Abidjan, Cote d’Ivoire, AIDS 4:443–448.PubMedCrossRefGoogle Scholar
  34. De Santis, C., Robbioni, P., Langhi, R., Lopalco, L., Siccardi, A. G., Beretta, A., and Roberts, N. J., Jr., 1993, Cross-reactive response to human immunodeficiency virus type 1 (HIV-1) gp120 and HLA class I heavy chains induced by receipt of HIV-1-derived envelope vaccines, J. Infect. Dis. 168:1396–1403.PubMedCrossRefGoogle Scholar
  35. de Wolf, F., Meloen, R. H., Bakker, M., Barin, R., and Goudsmit, J., 1991, Characterization of human antibody-binding sites on the external envelope of human immunodeficiency virus type 2, J. Gen. Virol. 72:1261–1267.PubMedCrossRefGoogle Scholar
  36. di Marzo Veronese, F., Rahman, R., Pal, R., Boyer, C., Romano, J., Kalyasaraman, U. S., Nair, B. C., Gallo, R. C., and Sarngadharan, M. G., 1992, Delineation of immunoreactive, conserved regions in the external envelope glycoprotein of the HIV-1, AIDS Res. Hum. Retrovir. 8:1125–1132.PubMedCrossRefGoogle Scholar
  37. di Marzo Veronese, F., Reitz, M. S., Jr., Gupta, G., Robert-Guroff, M., Boyer-Thompson, C., Louie, A., Gallo, R. C., and Lusso, P., 1993, Loss of a neutralizing epitope by a spontaneous point mutation in the V3 loop of HIV-1 isolated from an infected laboratory worker, J. Biol. Chem. 268:25894–25901.PubMedGoogle Scholar
  38. Dirckx, L., Lindemann, D., Ette, R., Manzoni, C., Moritz, D., and Mous, J., 1990, Mutation of conserved N-glycosylation sites around the CD4-binding site of human immunodeficiency virus type 1 gp120 affects viral infectivity, Virus Res. 18:9–20.PubMedCrossRefGoogle Scholar
  39. Ditzel, H. J., Binley, J. M., Moore, J. P., Sodroski, J., Sullivan, N., Sawyer, L. S., Hendry, R. M., Yang, W. P., Barbas, C. R., III, and Burton, D. R., 1995, Neutralizing recombinant human antibodies to a conformational V2 and CD4-binding site-sensitive epitope of HIV-1 gp120 isolated by using an epitope-masking procedure, J. Immunol. 154:893–906.PubMedGoogle Scholar
  40. Dowbenko, D., Nakamura, G., Fennie, C., Shimasaki, C., Riddle, L., Harris, R., Gregory, T., and Lasky, L., 1988, Epitope mapping of the human immunodeficiency virus type 1 gp120 with monoclonal antibodies, J. Virol. 62:4703–4711.PubMedGoogle Scholar
  41. Evans, L. A., Thomson-Honnebier, G., Steimer, K., Paoletti, E., Perkus, M. E., Hollander, H., and Levy, J. A., 1989, Antibody-dependent cellular cytotoxicity is directed against both the gp120 and gp41 envelope proteins of HIV, AIDS 3:273–276.PubMedCrossRefGoogle Scholar
  42. Felsenstein, J., 1985, Confidence limits on phylogenies: An approach using the bootstrap, Evolution 39:783–791.CrossRefGoogle Scholar
  43. Fung, M. S. C., Sun, C. R. Y., Gordon, W. L., Liou, R. S., Chang, T. W., Sun, W. N. C., Daar, E. S., and Ho, D. D., 1992, Identification and characterization of a neutralization site within the second variable region of human immunodeficiency virus type 1 gp120, J. Virol. 66:848–856.PubMedGoogle Scholar
  44. Gallaher, W. R., Ball, J. M., Garry, R. R., Griffin, M. C., and Montelaro, R. C., 1989, A general model for the transmembrane proteins of HIV and other retroviruses, AIDS Res. Hum. Retrovir. 5:431–440.PubMedCrossRefGoogle Scholar
  45. Gnann, J. W., Nelson, J. A., and Oldstone, M. B., 1987, Fine mapping of an immunodominant domain in the transmembrane glycoprotein of HIV, J. Virol. 61:2639–2641.PubMedGoogle Scholar
  46. Gody, M., Quattara, S. A., and de The, G., 1988, Clinical experience of AIDS in relation to HIV-1 and HIV-2 infection in a rural hospital in Ivory Coast, West Africa, AIDS 2:433–436.PubMedCrossRefGoogle Scholar
  47. Gorny, M. K., Xu, J. Y., Gianakakos, V., Karwowska, S., Williams, C., Sheppard, H. W., Hanson, C. V., and Zolla-Pazner, S., 1991, Production of site directed neutralizing human monoclonal antibodies against the third variable domain of the HIV-1 envelope glycoprotein, Proc. Natl. Acad. Sci. USA 88:3238–3241.PubMedCrossRefGoogle Scholar
  48. Gorny, M. K., Moore, J. P., Karwowska, S., Sodroski, J., Williams, C., Burda, S., Boots, L. J., and Zolla-Pazner, S., 1994, Human anti-V2 monoclonal antibody that neutralizes primary but not laboratory isolates of HIV-1, J. Virol. 68:8312–8320.PubMedGoogle Scholar
  49. Goudsmit, J., Boucher, C. A. B., Meloen, R. H., Epstein, L. G., Smit, L., van der Hoek, L., and Bakker, M., 1988, Human antibody response to a strain-specific HIV-1 gp120 epitope associated with cell fusion inhibition, AIDS 2:157–164.PubMedCrossRefGoogle Scholar
  50. Grassi, R., Meneveri, R., Gullberg, M., Lopalco, L., Rossi, G. B., Lanza, P., De Santis, C., Brattsand, G., Butto, S., Ginelli, E., Beraetta, A., and Siccardi, A. G., 1991, Human immunodeficiency virus type 1 gp120 mimics a hidden monomorphic epitope borne by class I major histocompatibility complex heavy chains, J. Exp. Med. 174:53–62.PubMedCrossRefGoogle Scholar
  51. Groenink, M., Fouchier, R. A., Broersen, S., Baker, C. H., Koot, M., van’t Wout, A. B., Huisman, H. G., Miedema, R., Tersmette, M., and Schuitemaker, H., 1993, Relation of phenotype evolution of HIV-1 to envelope V2 configuration, Science 260:1513–1516.PubMedCrossRefGoogle Scholar
  52. Grunow, R., Jahn, S., Porstmann, T., Kiessig, S. S., Steinkellner, S. H., Steindl, R., Mattanovich, D., Gurtler, L., Deinhardt, R., Katinger, H., and von Baehr, R., 1988, The high efficiency, human B cell immortalizing heteromyeloma CB-P7. Production of human monoclonal antibodies to human immunodeficiency virus, J. Immunol Methods 106:257–265.PubMedCrossRefGoogle Scholar
  53. Guyader, M., Emerman, M., Sonigo, P., Clavel, R., Montagnier, L., and Alizon, M., 1987, Genome organization and transactivation of the human immunodeficiency virus type 2, Nature 326:662–669.PubMedCrossRefGoogle Scholar
  54. Hahn, B. H., Shaw, G. M., Taylor, M. E., Redfield, R. R., Markham, P. D., Salahuddin, S. Z., Wong-Staal, R., Gallo, R. C., Parks, E. S., and Parks, W P., 1986, Genetic variation in HTLV-III/LAV over time in patients with AIDS, Science 232:1548–1553.PubMedCrossRefGoogle Scholar
  55. Ho, D. D., Sarngadharan, M. G., Hirsch, M. S., Schooley, R. T., Rota, T. R., Kennedy, R. C., Chanh, T. C., and Sato, V L., 1987, Human immunodeficiency virus neutralizing antibodies recognize several conserved domains on the envelope glycoproteins, J. Virol 61:2024–2028.PubMedGoogle Scholar
  56. Ho, D. D., Kaplan, I. E., Rackauskas, I. E., and Gurney, M. E., 1988, Second conserved domain of gp120 is important for viral infectivity and antibody neutralization, Science 239:1021–1023.PubMedCrossRefGoogle Scholar
  57. Ho, D. D., Fung, M. S., Cao, Y., Li, X. L., Sun, C., Chang, T. W., and Sun, N. C., 1991a, Another discontinuous epitope on glycoprotein gp120 that is important in HIV-1 neutralization is identified by a monoclonal antibody, Proc. Natl. Acad. Sci. USA 88:8849–8852.CrossRefGoogle Scholar
  58. Ho, D. D., McKeating, J. A., Li, X. L., Moudgil, T., Daar, E. S., Sun, N. C., and Robinson, J. E., 1991b, A conformational epitope on gp120 important in CD4 binding and HIV-1 neutralization identified by a human monoclonal antibody, J. Virol. 65:489–493.PubMedGoogle Scholar
  59. Holmes, E. C., Zhang, L. Q., Simmonds, P., Ludlam, C. A., and Leigh Brown, A. J., 1992, Convergent and divergent sequence evolution in the surface envelope glycoprotein of human immunodeficiency virus type 1 within a single infected patient, Proc. Natl. Acad. Sci. USA 89:4835–4839.PubMedCrossRefGoogle Scholar
  60. Horal, P., Svennerholm, B., Jeansson, S., Rymo, L., Hall, W. W., and Vahlne, A., 1991, Continuous epitopes of the HIV-1 transmembrane glycoprotein and reactivity of human sera to synthetic peptides representing various HIV-1 isolates, J. Virol. 65:2718–2723.PubMedGoogle Scholar
  61. Hoskins, T. W., Davies, J. R., Smith, A. J., Miller, C. L., and Allchin, A., 1979, Assessment of inactivated influenza-A vaccine after three outbreaks of influenza A at Christ’s Hospital, Lancet 1:33–35.PubMedCrossRefGoogle Scholar
  62. Javaherian, K., Langlois, A. J., McDanal, C., Ross, K. L., Eckler, L. I., Jellis, C. L., Profy, A. T., Rusche, J. R., Bolognesi, D. P., Putney, S. D., and Matthews, T. J., 1989, Principal neutralizing domain of the human immunodeficiency virus type 1 envelope protein, Proc. Natl. Acad. Sci. USA 86:6768–6772.PubMedCrossRefGoogle Scholar
  63. Javaherian, K., Langlois, A. J., LaRosa, G. J., Profy, A. T., Bolognesi, D. P., Herlihy, W. C., Putney, S. D., and Matthews, T. J., 1990, Broadly neutralizing antibodies elicited by the hypervariable neutralizing determinant of HIV-1, Science 250:1590–1593.PubMedCrossRefGoogle Scholar
  64. Jim, M. J., Hui, H., Robertson, D. L., Muller, M. C., Barré-Sinoussi, F., Hirsch, V. M., Allan, J. S., Shaw, P. M., and Hahn, B. H., 1994, Mosaic genome structure of simian immunodeficiency virus from West African green monkeys, EMBO J. 13:2935–2947.Google Scholar
  65. Jones, I. M., Morikawa, Y., Fenouillet, E., and Moore, J. P., 1992, Antigenicity of the HIV-2 V3 loop, AIDS 6:888–889.PubMedCrossRefGoogle Scholar
  66. Kang, C. Y., Nara, P., Chamat, S., Caralli, V., Ryskamp, T., Haigwood, N., Newman, R., and Kohler, H., 1991, Evidence for non V3 specific neutralizing antibodies that interfere with gp120/CD4 binding in human immunodeficiency infected humans, Proc. Natl. Acad. Sci. USA 88:6171–6175.PubMedCrossRefGoogle Scholar
  67. Kanki, P. J., M’Boup, S., Ricard, D., Barin, F., Denis, F., Boye, C., Sangare, L., Travers, K., Albaum, M., Marlink, R., Romet-Lemonne, J.-L., and Essex, M., 1987, Human T-lymphotropic virus type 4 and the human immunodeficiency virus in West Africa, Science 236:827–831.PubMedCrossRefGoogle Scholar
  68. Kanki, P., Travers, K., M’Boup, S., Hsieh, C.-C., Marlink, R. G., Guéye-Ndiaye, A., Siby, T., Thior, I., Herandez-Avila, M., Sankalé, J.-L., Ndoye, I., and Essex, M. E., 1994, Slower heterosexual spread of HIV-2 than HIV-1. Lancet 343:943–946.PubMedCrossRefGoogle Scholar
  69. Karwowska, S., Gorny, M. K., Buchbinder, A., and Zolla-Pazner, S., 1992a, Type-specific human monoclonal antibodies cross-react with the V3 loop of various HIV-1 isolates, in: Vaccines 92 (F. Brown, R. M. Chanock, H. S. Ginsberg, and R. A. Lerner, eds.), Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, p. 171.Google Scholar
  70. Karwowska, S., Gorny, M. K., Buchbinder, A., Gianakakos, V., Williams, C., Fuerst, T., and Zolla-Pazner, S., 1992b, Production of human monoclonal antibodies specific for conformational and linear non-V3 epitopes of gp120, AIDS Res. Hum. Retrovir. 8:1099–1106.PubMedCrossRefGoogle Scholar
  71. Kayman, S. C., Revesz, K., Chen, H., Kopelman, R., and Pinter, A., 1994, Presentation of native epitopes in the V1/V2 and V3 regions of human immunodeficiency virus type 1 gp120 by fusion glycoproteins containing isolated gp120 domains, J. Virol. 68:400–410.PubMedGoogle Scholar
  72. Keller, R., Peden, K., Paulous, S., Montagnier, L., and Cordonnier, A., 1993, Amino acid changes in the fourth conserved region of human immunodeficiency virus type 2 strain HIV-2ROD envelope glycoprotein modulate fusion, J. Virol. 67:6253–6258.PubMedGoogle Scholar
  73. Kennedy, R. C., Henkel, R. D., Pauletti, D., Allan, J. S., Lee, T. H., Essex, M., and Dreesman, G. R., 1986, Antiserum to a synthetic peptide recognizes the HTLV-III envelope glycoprotein, Science 231:1556–1559.PubMedCrossRefGoogle Scholar
  74. Klasse, P. J., Pipkorm, R., and Blomberg, J., 1988, Presence of antibodies to a putatively immunosuppressive part of HIV envelope glycoprotein gp41 is strongly associated with health among HIV-positive subjects, Proc. Natl. Acad. Sci. USA 85:5225–5229.PubMedCrossRefGoogle Scholar
  75. Koito, A., Harrowe, G., Levy, J. A., and Cheng-Mayer, C., 1994, Functional role of the V1/V2 region of human immunodeficiency virus type 1 envelope glycoprotein gp120 in infection of primary macrophages and soluble CD4 neutralization, J. Virol. 68:2253–2259.PubMedGoogle Scholar
  76. Kowalski, M., Potz, J., Basiripour, L., Dorfman, T., Goh, W. C., Terwilliger, E., Dayton, A., Rosen, C., Haseltine, W., and Sodroski, J., 1987, Functional regions of the envelope glycoprotein of human immunodeficiency virus type 1, Science 237:1351–1355.PubMedCrossRefGoogle Scholar
  77. Kusk, P., Holmback, K., Lindhardt, B. O., Hulgaard, E. R., and Bugge, T. H., 1992, Mapping of two new human B-cell epitopes on HIV-1 gp120, AIDS 6:1451–1456.PubMedCrossRefGoogle Scholar
  78. Lane, H. C., Masur, H., Edgar, L. C., Whalen, G., Rook, A. H., and Fauci, A. S., 1983, Abnormalities of B-cell activation and immunoregulation in patients with acquired immunodeficiency syndrome, N. Engl. J. Med. 309:453–458.PubMedCrossRefGoogle Scholar
  79. LaRosa, G. J., Davide, J. P., Weinhold, K., Waterbury, J., Profy, A., Lewis, J., Langlois, A., Dreesman, G., Boswell, R., Shadduck, P., Holley, L., Karplus, M., Bolognesi, D., Matthews, T., Emini, E., and Putney, S., 1990, Conserved sequence and structural elements in the HIV-l principal neutralizing determinant, Science 249:932–935.PubMedCrossRefGoogle Scholar
  80. Lasky, L. A., Nakamura, G., Smith, D. H., Fennie, C., Shimasaki, C., Patzer, E., Berman, P., Gregory, T., and Capon, D. J., 1987, Delineation of a region of the human immunodeficiency virus type 1 gp120 glycoprotein critical for interaction with the CD4 receptor, Cell 50:975–985.PubMedCrossRefGoogle Scholar
  81. Leonard, C. K., Spellman, M. W., Riddle, L., Harris, R. J., Thomas, J. N., and Gregory, T. J., 1990, Assignment of intrachain disulfide bonds and characterization of potential glycosylation sites of the type 1 recombinant human immunodeficiency virus envelope glycoprotein (gp120) expressed in Chinese hamster ovary cells, J. Biol. Chem. 265:10373–10382.PubMedGoogle Scholar
  82. Levy, J., 1993, Pathogenesis of human immunodeficiency virus infection, Microbiol. Rev. 57:183–289.PubMedGoogle Scholar
  83. Lopalco, L., De Santis, C., Meneveri, R., Longhi, R., Ginelli, E., Grassi, F., Siccardi, A. G., and Beretta, A., 1993, Human immunodeficiency virus type 1 gp120 C5 region mimics the HLA class alpha-1 peptide-binding domain, Eur. J. Immunol. 23:2016–2021.PubMedCrossRefGoogle Scholar
  84. Louwagie, J., McCutchan, R E., Peeters, M., Brennan, T. P., Sanders-Buell, E., Eddy, G. A., van der Groen, G., Fransen, K., Gershy-Damet, G.-M., Deleys, R., and Burke, D. S., 1993, Phylogenetic analysis of gag genes from 70 international HIV-1 isolates provides evidence for multiple genotypes, AIDS 7:769–780.PubMedCrossRefGoogle Scholar
  85. Luo, L., Li, Y., Cannon, P. M., Kim, S., and Yong Kang, C., 1992, Chimeric gag-V3 virus-like particles of human immunodeficiency virus induce virus neutralizing antibodies, Proc. Natl. Acad. Sci. USA 89:10527–10531.PubMedCrossRefGoogle Scholar
  86. McKeating, J., Thali, M., Furman, C., Karwowska, S., Gorny, M. K., and Cordell, J., 1992a, Amino acid residues of the HIV-1 gp120 critical for binding of rat and human neutralizing antibodies that block the gp120-sCD4 interaction, Virology 190:134–142.PubMedCrossRefGoogle Scholar
  87. McKeating, J., Moore, J., Ferguson, M., Marsden, H. S., Graham, S., Almond, J. W., Evans, D. J., and Weiss, R. A., 1992b, Monoclonal antibodies to the C4 region of HIV-1 gp120: Use in topological analysis of a CD4 binding site. AIDS Res. Hum. Retrovir. 8:451–459.PubMedCrossRefGoogle Scholar
  88. McKeating, J. A., Shotton, C., Cordell, J., Graham, S., Balfe, P., Sullivan, N., Charles, M., Page, M., Blomstedt, A., Olofsson, S., Kayman, S. C., Wu, Z., Pinter, A., Dean, C., Sodroski, J., and Weiss, R. A., 1993, Characterization of neutralizing monoclonal antibodies to linear and conformation-dependent epitopes within the first and second variable domains of human immunodeficiency virus type 1 gp120, J. Virol. 67:4932–4944.PubMedGoogle Scholar
  89. Mannervik, M., Putkonen, P., Ruden, U., Kent, K. A., Norrby, E., Wahren, B., and Broliden, P.-A., 1992, Identification of B-cell antigenic sites on HIV-2 gp125, J. Acq. Immune Defic. Syndr. 5:177–187.Google Scholar
  90. Marlink, R., Kanki, P., Thior, I., Travers, K., Eisen, G., Siby, T., Traore, I., Hsieh, C.-C., Dia, M. C., Gueye, E. H., Hellinger, J., Gueyé-Ndiaye, A., Sankalé, J.-L., Ndoye, I., Mboup, S., and Essex, M., 1994, Reduced rate of disease development after HIV-2 infection as compared to HIV-1 Science 265:1587–1590.PubMedCrossRefGoogle Scholar
  91. Matsushita, S., Matsumi, S., Yoshimura, K., Morikita, T., Murakami, T., and Takatsuki, K., 1995, Neutralizing monoclonal antibodies against human immunodeficiency virus type 2 gp120, J. Virol. 69:3333–3340.PubMedGoogle Scholar
  92. Matthews, T. J., Langlois, A. J., Robey, W. G., Chang, N. T., Gallo, R. C., Fischinger, P. J., and Bolognesi, D. P., 1986, Restricted neutralization of divergent human T-lymphotropic virus type III isolates by antibodies to the major envelope glycoprotein, Proc. Natl. Acad. Sci. USA 83:9709–9713.PubMedCrossRefGoogle Scholar
  93. Meyerhans, A., Cheynier, R., Albert, J., Seth, M., Kwok, S., Sninsky, J., Morfeldt-Månson, L., Åsjo, B., and Wain-Hobson, S., 1989, Temporal fluctuations in HIV quasispecies in vivo are not reflected by sequential HIV isolations, Cell 58:901–910.PubMedCrossRefGoogle Scholar
  94. Michel, M. L., Mancini, M., Sobczak, E., Favier, V., Guetard, D., Bahraoui, E. M., and Tollais, P., 1988, Induction of anti human immunodeficiency virus (HIV) neutralizing antibodies in rabbits immunized with recombinant HIV-hepatitis B surface antigen particle, Proc. Natl. Acad. Sci. USA 85:7957–7960.PubMedCrossRefGoogle Scholar
  95. Modrow, S., Hahn, B. H., Shaw, G. M., Gallo, R. C., Wong-Staal, R., and Wolf, H., 1987, Computer assisted analysis of envelope protein sequences of seven human immunodeficiency virus isolates: Prediction of antigenic epitopes in conserved and variable regions, J. Virol. 61:570–578.PubMedGoogle Scholar
  96. Moore, J. P., and Ho, D. D., 1993, Antibodies to discontinuous or conformationally sensitive epitopes on the gp120 glycoprotein of HIV type 1 are highly prevalent in sera of infected humans, J. Virol. 67:863–867.PubMedGoogle Scholar
  97. Moore, J., Sattentau, Q., Yoshiyama, H., Thali, M., Charles, M., Sullivan, N., Poon, S.-W., Fung, M. S., Traincard, F., Pincus, M., Robey, G., Robinson, J. E., Ho, D. D., and Sodroski, J., 1993a, Probing the structure of the V2 domain of HIV type 1 surface glycoprotein gp120 with a panel of eight monoclonal antibodies: Human immune response to the V1 and V2 domains, J. Virol. 67:6136–6151.PubMedGoogle Scholar
  98. Moore, J. P., Thali, M., Jameson, B. A., Vignaux, F., Lewis, G. K., Poon, S. W., Charles, M. A., Fung, M. S., Sun, B., Durda, P. M., Akerblom, L., Wahren, B., Ho, D. D., Sattentau, Q., and Sodroski, J., 1993b, Immunochemical analysis of the gp120 surface glycoprotein of human immunodeficiency virus type 1: Probing the structure of the C4 and V4 domains and the interaction of the C4 domain with the V3 loop, J. Virol. 67:4785–4796.PubMedGoogle Scholar
  99. Moore, J. P., McCutchan, F. E., Poon, S. W., Mascola, J., Liu, J., Cao, Y., and Ho, D. D., 1994, Exploration of antigenic variation in gp120 from clades A through F of human immunodeficiency virus type 1 by using monoclonal antibodies, J. Virol. 68:8350–8364.PubMedGoogle Scholar
  100. Murphey-Corb, M., Martin, L. N., Rangan, S. R., Baskin, G. B., Gormus, B. J., Wolf, R. H., Andes, W A., West, M., and Montelaro, R. C., 1986, Isolation of an HTLV-III related retrovirus from macaques with simian AIDS and its possible origin in asymptomatic mangabeys, Nature 321:435–437.PubMedCrossRefGoogle Scholar
  101. Muster, T., Guinea, R., Trkola, A., Purtscher, M., Klima, A., Steindl, F., Palese, P., and Katinger, H., 1994, Cross-neutralizing activity against divergent human immunodeficiency virus type 1 isolates induced by the gp41 sequence ELDKWAS, J. Virol. 68:4031–4034.PubMedGoogle Scholar
  102. Myers, G., Korber, B., Smith, R. R., Berzofsky, J. A., and Pavlakis, G. N., 1992, Human Retroviruses and AIDS 1992, Los Alamos National Laboratory, Los Alamos, NM.Google Scholar
  103. Myers, G., Korber, B., Smith, R. F., Berzofsky, J. A., and Pavlakis, G. N., 1993, Human Retroviruses and AIDS 1993, Los Alamos National Laboratory, Los Alamos, NM.Google Scholar
  104. Myers, G., Korber, B., Jeang, K. T., Henderson, L., Wain-Hobson, S., and Pavlakis, G. N., 1994, Human Retroviruses and AIDS 1994, Los Alamos National Laboratory, Los Alamos, NM.Google Scholar
  105. Myers, G., Rabson, A. B., Berzofsky, J. A., Smith, T. F., and Wong-Staal, F., 1990, Human Retroviruses and AIDS 1990, Los Alamos National Laboratory, Los Alamos, NM.Google Scholar
  106. Nakamura, G. R., Byrn, R., Rosenthal, K., Porter, J. P., Hobbs, M. R., Riddle, L., Eastman, D. J., Dowbenko, D., Gregory, T., Fendly, B. M., and Berman, P. W., 1992, Monoclonal antibodies to the extracellular domain of HIV-1 IIIB gp160 that neutralize infectivity, block binding to CD4 and react with diverse isolates, AIDS Res. Hum. Retrovir. 8:1875–1885.PubMedCrossRefGoogle Scholar
  107. Nara, P. L., Robey, W G., Arthur, L. O., Asher, D. M., Wolff, A. V., Gibbs, C. J., Jr., Gajdusek, D. C., and Fischinger, P. J., 1987, Persistent infection of chimpanzees with HIV: Serological responses and properties in re-isolated viruses, J. Virol 61:3173–3180.PubMedGoogle Scholar
  108. Nara, P. L., Smith, L., Dunlop, N., Hatch, W., Merges, M., Waters, D., Kelliher, J., Gallo, R. C., Fischinger, P. J., and Goudsmit, J., 1990, Emergence of viruses resistant to neutralization by V3 specific antibodies in experimental human immunodeficiency virus type 1 IIIB infection of chimpanzees, J. Virol. 64:3779–3791.PubMedGoogle Scholar
  109. Neurath, A. R., 1993, B cell antigenic site mapping of HIV-1 glycoproteins, in: Chemical Immunology, Volume 56 (L. Aldorini, B. Arai, F. W. Fitch, K. Ishizaka, P. J. Lachmann, and B. H. Waksman, eds.), Karger, Basel, pp. 34–60.Google Scholar
  110. Niedrig, M., Harthus, H. P., Hinkula, J., Broker, M., Bickhard, H., Pauli, G., Gelderblom, H. R., and Wahren, B., 1992, Inhibition of viral replication by monoclonal antibodies directed against HIV gp120, J. Gen. Virol. 73:2451–2455.PubMedCrossRefGoogle Scholar
  111. Norrby, E., Biberfeld, G., Chiodi, F., von Gegerfelt, A., Naucler, A., Parks, E., and Lerner, R., 1987, Discrimination between antibodies to HIV and to related retroviruses using site-directed serology, Nature 329:248–250.PubMedCrossRefGoogle Scholar
  112. Norrby, E., Parks, D. E., Utter, G., Houghten, R. A., and Lerner, R. A., 1989, Immunochemistry of the dominating antigenic region Ala582 to Cys604 in the transmembranous protein of simian and human immunodeficiency virus, J. Immunol. 143:3602–3608.PubMedGoogle Scholar
  113. Norrby, E., Putkonen, P., Böttiger, B., Utter, G., and Biberfeld, G., 1991, Comparison of linear antigenic sites in the envelope proteins of human immunodeficiency virus (HIV) type 2 and type 1, AIDS Res. Hum. Retrovir. 7:279–285.PubMedCrossRefGoogle Scholar
  114. Nowak, M. A., Anderson, R. A., McLean, A. R., Wolfs, T. E. W., Goudsmit, J., and May, R. M., 1991, Antigenic diversity thresholds and the development of AIDS, Science 254:963–969.PubMedCrossRefGoogle Scholar
  115. Oldstone, M. B., Tishon, A., Lewicki, H., Dyson, H. J., Feher, V A., Assa-Munt, N., and Wright, P. E., 1991, Mapping the anatomy of the immunodominant domain of the HIV gp41 transmembrane protein: Peptide conformation analysis using monoclonal antibodies and proton nuclear magnetic resonance spectroscopy, J. Virol. 65:1727–1734.PubMedGoogle Scholar
  116. Olshevsky, U., Helseth, E., Furman, C., Li, J., Haseltine, W., and Sodroski, J., 1990, Identification of individual human immunodeficiency virus type 1 gp120 amino acids important for CD4 receptor binding, J. Virol. 64:5701–5707.PubMedGoogle Scholar
  117. Palker, T. J., Matthews, T. J., Clark, M. E., Ciancole, G. J., Randall, R. R., Langlois, A. J., White, G. C., Safai, B., Snyderman, R., Bolognesi, D. P., and Haynes, B. F., 1987, A conserved region at the COOH terminus of human immunodeficiency virus gp120 envelope protein contains an immunodominant epitope, Proc. Natl. Acad. Sci. USA 84:2479–2483.PubMedCrossRefGoogle Scholar
  118. Palker, T. J., Matthews, T. J., Langlois, A., Tanner, M. E., Martin, M. E., Scearce, R. M., Kim, J. E., Berzofsky, J. A., Bolognesi, D. P., and Haynes, B. R., 1989, Polyvalent human immunodeficiency virus synthetic immunogen comprised of envelope gp120 T helper cell sites and B cell neutralization epitopes, J. Immunol. 142:3612–3619.PubMedGoogle Scholar
  119. Pincus, S. H., Messer, K. G., Nara, P. L., Blattner, W. A., Colclough, G., and Reitz, M., 1994, Temporal analysis of the antibody response to HIV envelope protein in HIV-1 infected laboratory workers, J. Clin. Invest. 93:2505–2513.PubMedCrossRefGoogle Scholar
  120. Popovic, M., Sarngadharan, M. G., Read, E., and Gallo, R. C., 1984, Detection, isolation, and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS, Science 224:497–500.PubMedCrossRefGoogle Scholar
  121. Posner, M., Hideshima, T., Cannon, T., Mukherjee, M., Mayer, K. H., and Byrn, R. A., 1991, An IgG human monoclonal antibody which reacts with HIV-1 gp120 inhibits virus binding to cells, and neutralizes infection, J. Immunol 146:4325–4332.PubMedGoogle Scholar
  122. Posner, M. R., Cavacini, L. A., Ernes, C., Power, J., and Byrn, R., 1993, Neutralization of HIV-1 by F105, a human monoclonal antibody to the CD4 binding site of gp120, J. Acq. Immune Defic. Syndr. 6:7–14.Google Scholar
  123. Profy, A., Salinas, P., Eckler, L., Dunlop, N., Nara, P., and Putney, S., 1990, Epitopes recognized by the neutralizing antibodies of an HIV-1-infected individual, J. Immunol. 144:4641–4647.PubMedGoogle Scholar
  124. Putney, S. D., Matthews, T. J., Robey, W. G., Lynn, D. L., Robert-Guroff, M., Mueller, W. T., Langlois, A., Ghrayeb, J., Petteway, S. R., Weinhold, K. J., Fischinger, P. J., Wong-Staal, F., Gallo, R. C., and Bolognesi, D. P., 1986, HTLV-III/LAV-neutralizing antibodies to an E. coli-produced fragment of the virus envelope, Science 234:1392–1395.PubMedCrossRefGoogle Scholar
  125. Ranki, A., Weiss, S. H., Valle, S. L., Antonen, J., and Krohn, K. J. E., 1987, Neutralizing antibodies in HIV (HTLV-III) infection: Correlation with clinical outcome and antibody response against different viral proteins, Clin. Exp. Immunol. 69:231–239.PubMedGoogle Scholar
  126. Roben, P., Moore, J. P., Thali, M., Sodroski, J., Barbas, C. F., III, and Burton, D. R., 1994, Recognition properties of a panel of human recombinant Fab fragments to the CD4 binding site of gp120 that show differing abilities to neutralize human immunodeficiency virus type 1, J. Virol. 68:4821–4828.PubMedGoogle Scholar
  127. Robert-Guroff, M., Brown, M., and Gallo, R. C., 1985, HTLV-III neutralizing antibodies in patients with AIDS and AIDS related complex, Nature 316:72–74.PubMedCrossRefGoogle Scholar
  128. Robert-Guroff, M., Aldrich, K., Muldoon, R., Stern, T. L., Bansal, G. P., Matthews, T. J., Markham, P. D., Gallo, R. C., and Franchini, G., 1992, Cross-neutralization of human immunodeficiency virus type 1 and 2 and simian immunodeficiency virus isolates, J. Virol. 66:3602–3608.PubMedGoogle Scholar
  129. Robey, W G., Safai, B., Oroszlan, S., Arthur, L. O., Gonda, M. A., Gallo, R. C., and Fischinger, P. J., 1985, Characterization of envelope and core structural gene products of HTLV-III with sera from AIDS patients, Science 228:593–595.PubMedCrossRefGoogle Scholar
  130. Robey, W. G., Arthur, L. O., Matthews, T. J., Langlois, A., Copeland, T. D., Lerche, N. W., Oroszlan, S., Bolognesi, D. P., Gilden, A. V., and Fischinger, P. J., 1986, Prospect for prevention of human immunodeficiency virus infection: Purified 120kDa envelope glycoprotein induces neutralizing antibody, Proc. Natl. Acad. Sci. USA 83:7023–7027.PubMedCrossRefGoogle Scholar
  131. Robinson, W. E., Jr., Gorny, M. K., Xu, J. Y., Mitchell, W M., and Zolla-Pazner, S., 1991, Two immunodominant domains of gp41 bind antibodies which enhance HIV-1 infection in vitro, J. Virol. 65:4169–4176.PubMedGoogle Scholar
  132. Rusche, J. R., Javaherian, K., McDanal, C., Petro, J., Lynn, D. L., Grimalia, R., Langlois, A., Gallo, R. C., Arthur, L. O., Fischinger, P. J., Bolognesi, D. P., Putney, S., and Matthews, T. J., 1988, Antibodies that inhibit fusion of HIV-1 infected cells bind to 24 amino acid sequence of the viral envelope, gp120, Proc. Natl. Acad. Sci. USA 85:3198–3202.PubMedCrossRefGoogle Scholar
  133. Saag, M. S., Hahn, B. H., Gibbons, J., Li, Y., Parks, E. S., Parks, W. P., and Shaw, G. M., 1988, Extensive variation of human immunodeficiency virus type 1 in vivo, Nature 334:440–444.PubMedCrossRefGoogle Scholar
  134. Sattentau, Q. J., Clapham, P., Weiss, R. A., Beverly, P., Montagnier, L., Alhalabi, M. F., Gluckmann, J. C., and Klatzmann, D., 1988, The human and simian immunodeficiency viruses HIV-1, HIV-2 and SIV interact with similar epitopes in their cellular receptor, the CD4 molecule, AIDS 2:101–105.PubMedCrossRefGoogle Scholar
  135. Schrier, R. D., Gnann, J. W., Jr., Langlois, A. J., Shriver, K., Nelson, J. A., and Oldstone, M. B., 1988, B and T-lymphocyte responses to an immunodominant epitope of human immunodeficiency virus, J. Virol. 62:2531–2536.PubMedGoogle Scholar
  136. Scott, C. F., Jr., Silver, S., Profy, A. T., Putney, S.D., Langlois, A., Weinhold, K., and Robinson, J. E., 1990, Human monoclonal antibody that recognizes the V3 region of HIV gp120 and neutralizes the human T-lymphotropic virus type III-MN strain, Proc. Natl. Acad. Sci. USA 87:8597–8600.PubMedCrossRefGoogle Scholar
  137. Sharp, P. M., Robertson, D. L., Gao, R., and Hahn, B. H., 1994, Origins and diversity of human immunodeficiency viruses, AIDS 8(Suppl. 1):S27–S42.Google Scholar
  138. Shotton, C., Arnold, C., Sattentau, Q., Sodroski, J., and McKeating, J. A., 1995, Identification and characterization of monoclonal antibodies specific for polymorphic antigenic determinants within the V2 region of the human immunodeficiency virus type 1 envelope glycoprotein, J. Virol. 69:222–230.PubMedGoogle Scholar
  139. Simmonds, P., Zhang, L. Q., McOmish, F., Balfe, P., Ludlam, C. A., and Leigh Brown, A. J., 1991, Discontinuous sequence change of human immunodeficiency virus (HIV) type 1 env sequences in plasma viral and lymphocyte-associated proviral populations in vivo: Implications for models of HIV pathogenesis, J. Virol 65:6266–6275.PubMedGoogle Scholar
  140. Sodroski, J., Goh, W. C., Rosen, K., Campbell, K., and Haseltine, W. A., 1986. Role of the HTLV-III/LAV envelope in syncytium formation and cytopathicity, Nature 322:470–474.PubMedCrossRefGoogle Scholar
  141. Stamatatos, L., and Cheng-Mayer, C., 1993, Evidence that the structural conformation of envelope gp120 affects human immunodeficiency virus type 1 infectivity, host range and syncytium forming ability, J. Virol. 67:5635–5639.PubMedGoogle Scholar
  142. Steimer, K. S., Scandella, C. J., Stiles, P. V., and Haigwood, N. L., 1991, Neutralization of divergent HIV-1 isolates by conformation dependent human antibodies to gp 120, Science 254:105–108.PubMedCrossRefGoogle Scholar
  143. Sugano, T., Musuho, Y., Matsumoto, Y., Lake, D., Gschwind, C., Petersen, E. A., and Hersh, E. M., 1988, Human monoclonal antibody against glycoproteins of human immunodeficiency virus, Biochem. Biophys. Res. Commun. 155:1105–1112.PubMedCrossRefGoogle Scholar
  144. Sullivan, N., Thali, M., Furman, C., Ho, D. D., and Sodroski, J., 1993, Effect of amino acid changes in the V1/V2 region of the human immunodeficiency virus type 1 gp120 glycoprotein on subunit association, syncytium formation, and recognition by a neutralizing antibody, J. Virol. 67:3674–3679.PubMedGoogle Scholar
  145. Sun, N. C., Ho, D. D., Sun, C. R., Liou, R. S., Gordon, W., Fung, M. S., Li, X. L., Ting, R. C., Lee, T. H., Chang, N. T., and Chang, T.-W., 1989, Generation and characterization of monoclonal antibodies to the putative CD-4-binding domain of HIV-1 gp120, J. Virol. 63:3579–3585.PubMedGoogle Scholar
  146. Teeuwsen, V. J. P., Sieblink, K. H. J., Crush-Stanton, S., Swerdlow, B., Schalken, J. J., Goudsmir, J., van de Akker, R., Stukart, M. J., Vytdehaag, F. G., and Osterhaus, A. D., 1990, Production and characterization of a human monoclonal antibody, reactive with a conserved epitope on gp41 of human immunodeficiency virus type 1, AIDS Res. Hum. Retrovir. 6:381–392.PubMedCrossRefGoogle Scholar
  147. Thali, M., Olshevsky, U., Furman, C., Gabuzda, D., Posner, M., and Sodroski, J., 1991, Characterization of a discontinuous HIV-1 gp120 epitope recognized by a broadly reactive neutralizing human monoclonal antibody, J. Virol. 65:6188–6193.PubMedGoogle Scholar
  148. Thali, M., Furman, C., Ho, D. D., Robinson, J., Tilley, S., Pinter, A., and Sodroski, J., 1992, Discontinuous conserved neutralization epitopes overlapping the CD4 binding region of the HIV-1 gp120 envelope glycoprotein, J. Virol. 66:5635–5641.PubMedGoogle Scholar
  149. Tilley, S. A., Honnen, W. J., Racho, M., Hilgartner, M., and Pinter, A., 1991, A human monoclonal antibody against CD4 binding site of HIV-1 gp120 exhibits potent, broadly neutralizing activity, Res. Virol. 142:247–259.PubMedCrossRefGoogle Scholar
  150. Toile, T., Petry, H., Bachmann, B., Hunsmann, G., and Luke, W., 1994, Variability of the env gene in cynomolgus macaques persistently infected with human immunodeficiency virus type 2 strain ben, J. Virol. 68:2765–2771.Google Scholar
  151. Traincard, R., Rey-Cuille, M. A., Huon, I., Dartevelle, S., Mazie, J. C., and Benichou, S., 1994, Characterization of monoclonal antibodies to human immunodeficiency virus type 2 envelope glycoproteins, AIDS Res. Hum. Retrovir. 10:1659–1667.PubMedCrossRefGoogle Scholar
  152. Travers, K., Mboup, S., Marlink, R., Guéye-Ndiaye, A., Siby, T., Thior, I., Traore, I., Dieng-Sarr, A., Sankalé, J.-L., Mullins, C. Ndoye, I., Hsieh, C.-C., Essex, M., and Kanki, P., 1995, Natural protection against HIV-1 infection provided by HIV-2, Science 268:1612–1615.PubMedCrossRefGoogle Scholar
  153. Tremblay, M., and Weinberg, M. A., 1990, Neutralization of multiple HIV-1 isolates from a single subject by autologous sequential sera, J. Infect. Dis. 162:735–737.PubMedCrossRefGoogle Scholar
  154. Tyler, D. S., Stanley, S. D., Zolla-Pazner, S., Gorny, M. K., Shadduck, P., Langlois, A. J., Matthews, T. J., Bolognesi, D. P., Palker, T. J., and Weinhold, K. J., 1990, Identification of sites within gp41 that serve as targets for antibody-dependent cellular cytotoxicity by using human monoclonal antibodies, J. Immunol. 145:3276–3282.PubMedGoogle Scholar
  155. Vanini, S., Longhi, R., Lazzarin, A., Vigo, E., Siccardi, A. G., and Viale, G., 1993, Discrete regions of HIV-1 gp41 defined by syncytia-inhibiting affinity-purified human antibodies, AIDS 7:167–174.PubMedCrossRefGoogle Scholar
  156. van Tijn, D. A., Boucher, C. A., Bakker, M., and Goudsmit, J., 1989, Antigenicity of linear B cell epitopes in the C1, V1 and V3 region of HIV-1 gp120, J. Acq. Immune Defic. Syndr. 2:303–306.Google Scholar
  157. Vogel, T., Kurth, R., and Norley, S., 1994, The majority of neutralizing Abs in HIV-1 infected patients recognize linear V3-loop sequences. Studies using HIV-1MN multiple antigenic peptides, J. Immunol. 153:1895–1904.PubMedGoogle Scholar
  158. von Gegerfelt, A., Albert, J., Morfeldt-Månson, L., Broliden, K., and Fenyö, E.-M., 1991, Isolate-specific neutralizing antibodies in patients with progressive HIV-1-related disease, Virology 185:162–168.CrossRefGoogle Scholar
  159. Warrier, S. V., Pinter, A., Honnen, W. J., Girard, M., Muchmore, E., and Tilley, S. A., 1994, A novel, glycan-dependent epitope in the V2 domain of human immunodeficiency virus type 1 gp120 is recognized by a highly potent, neutralizing chimpanzee monoclonal antibody, J. Virol 68:4636–4642.PubMedGoogle Scholar
  160. Weiss, R. A., Clapham, P. R., Weber, J., Cheingsong-Popov, R., Dalgleish, A., Carne, A., Weiler, I., and Tedder, R. S., 1985, Neutralisation of human T-lymphotropic virus type III by sera of AIDS and AIDS-risk patients, Nature 316:69–72.PubMedCrossRefGoogle Scholar
  161. Weiss, R. A., Clapham, P. R., Weber, J. N. N., Dalgleish, A. G., Lasky, L. A., and Berman, P. W., 1986, Variable and conserved neutralization antigens of HIV, Nature 324:572–575.PubMedCrossRefGoogle Scholar
  162. Weiss, R. A., Clapham, P., Weber, J. N., Whitby, D., Tedder, R. S., O’Connor, T., Chamaret, S., and Montagnier, L., 1988, HIV-2 antisera cross-neutralise HIV-1, AIDS 2:95–100.PubMedCrossRefGoogle Scholar
  163. Westervelt, P., Trowbridge, D. B., Epstein, L. G., Blumberg, B. M., Li, Y., Hahn, B. H., Shaw, G. M., Price, R. W., and Ratner, L., 1992, Macrophage tropism determinants of human immunodeficiency virus type 1 in vivo, J. Virol. 66:2577–2582.PubMedGoogle Scholar
  164. Willey, R. L., Rutledge, R. A., Dias, S., Folks, T., Theodore, T., Buckler, C. E., and Martin, M. A., 1986, Identification of conserved and divergent domains within the envelope gene of the acquired immunodeficiency syndrome retrovirus, Proc. Natl. Acad. Sci. USA 83:5038–5042.PubMedCrossRefGoogle Scholar
  165. Willey, R. L., Smith, L. A., Lasky, L. A., Theodore, T. S., Earl, P. L., Moss, B., Capon, D. J., and Martin, M. A., 1988, In vitro mutagenesis identifies a region within the envelope gene of the human immunodeficiency virus that is critical for infectivity, J. Virol. 62:139–147.PubMedGoogle Scholar
  166. Xu, J. Y., Gorny, M. K., Palker, T., Karwowska, S., and Zolla-Pazner, S., 1991, Epitope mapping of two immunodominant domains of gp41, the transmembrane protein of HIV-1, using 10 human monoclonal antibodies, J. Virol. 65:4832–4838.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Ewa Björling
    • 1
  • Erling Norrby
    • 1
  1. 1.Microbiology and Tumorbiology CenterKarolinska InstituteStockholmSweden

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