Inhibiting sexual transmission of HIV-1 infection

Nature Reviews Microbiology

Volumn 1, Issue 1, 2003, Pages 25-34

  Shattock, Robin J ^a   Moore, John P ^b  

^a ST GEORGE'S UNIVERSITY OF LONDON   (United Kingdom)

^b WEILL CORNELL MEDICAL COLLEGE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; ANTIINFECTIVE AGENT; HUMAN IMMUNODEFICIENCY VIRUS FUSION INHIBITOR; VIRUS ENVELOPE PROTEIN;

ANIMAL; DISEASE TRANSMISSION; DRUG ANTAGONISM; DRUG DELIVERY SYSTEM; EPITHELIUM CELL; FEMALE; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; INTRAVAGINAL DRUG ADMINISTRATION; MALE; RECTAL DRUG ADMINISTRATION; RECTUM; REVIEW; VAGINA; VIROLOGY;

ADMINISTRATION, INTRAVAGINAL; ADMINISTRATION, RECTAL; ANIMALS; ANTI-HIV AGENTS; ANTI-INFECTIVE AGENTS; DISEASE TRANSMISSION, HORIZONTAL; DRUG DELIVERY SYSTEMS; EPITHELIAL CELLS; FEMALE; GENE PRODUCTS, ENV; HIV FUSION INHIBITORS; HIV INFECTIONS; HIV-1; HUMANS; MALE; RECTUM; VAGINA;

EID: 0345569681     PISSN: 17401526     EISSN: 17401534     Source Type: Journal    
DOI: 10.1038/nrmicro729     Document Type: Article

References (126)

1. UN AIDS. AIDS Epidemic Update, (2002).
2. Vittinghoff, E. et al. Per-contact risk of human immunodeficiency virus transmission between male sexual partners. Am. J. Epidemiol. 150, 306-311 (1999).
3. Padian, N., Shiboski, S. Glass, S. & Vittinghoff, E. Heterosexual transmission of human immunodeficiency virus (HIV) in northern California: results of a ten-year study Am. J. Epidemiol. 146, 350-357 (1997).
4. Gray, R. H. et al. Probability of HIV-1 transmission per coital act in monogamous, heterosexual, HIV-1-discordant couples in Rakai, Uganda. Lancet 357, 1149-1153 (2001).
5. Auvert, B. et al. Ecological and individual level analysis of risk factors for HIV infection in four urban populations in sub-Saharan Africa with different levels of HIV infection. AIDS 15, S15-S30 (2001).
6. de Vincenzi, I. A longitudinal study of human immunodeficiency virus transmission by heterosexual partners. European Study Group on Heterosexual Transmission of HIV. N. Engl. J. Med. 331, 341-346 (1994).
7. Nicolosi, A. et al. The efficiency of male-to-female and female-to-male sexual transmission of the human immunodeficiency virus: a study of 730 stable couples. Italian Study Group on HIV Heterosexual Transmission. Epidemiology 5, 570-575 (1994).
8. Mastro, T. D., Satten, G. A., Nopkesorn, T., Sangkharomya, S. & Longini, I. M. Jr Probability of female-to-male transmission of HIV-1 in Thailand. Lancet 343, 204-207 (1994).
9. Halperin, D. T. Heterosexual anal intercourse: prevalence, cultural factors, and HIV infection and other health risks, Part I. AIDS Patient Care STDs. 13, 717-730 (1999).
10. Baleta, A. Concern voiced over 'dry sex' practices in South Africa. Lancet 352, 12-92 (1998).
11. Miller, C. J. & Shattock, R. J. Target cells in vaginal HIV transmission. Microbes Infect. 5, 59-67 (2003).
12. Quinn, T. C. et al. Viral load and heterosexual transmission of human immunodeficiency virus type 1. N. Engl. J. Med. 342, 921-929 (2000).
13. Eron, J. J. Jr et al. The effects of protease inhibitor therapy on human immunodeficiency virus type 1 levels in semen (AIDS clinical trials group protocol 850). J. Infect. Dis. 181, 29. 1622-1628 (2000).
14. Cu-Uvin, S. et al. Effect of highly active antiretroviral therapy on cervicovaginal HIV-1 RNA. AIDS 14, 415-421 (2000).
15. Kalichman, S. C. et al. Human immunodeficiency virus in semen and plasma: investigation of sexual transmission risk 31. behavioral correlates. AIDS Res. Hum. Retroviruses 17, 1695-1703 (2001).
16. Tachet, A. et al. Detection and quantification of HIV-1 in semen: identification of a subpopulation of men at high potential risk of viral sexual transmission. AIDS 13, 823-831 32. (1999).
17. Wawer, M. J. et al. HIV-1 transmission per coital act, by stage of HIV infection in the HIV+ index partner in discordant couples, Rakai, Uganda. 10th Conference on Retroviruses 33. and Opportunistic Infections, [online] (cited 12 Aug 2003), (2003).
18. Zhang, L. Q. et al. Selection for specific sequences in the external envelope protein of human immunodeficiency virus type 1 upon primary infection. J. Virol. 67, 3345-3356 (1993).
19. Fiore, A. J. et al. Biological phenotype of HIV-1 and transmission. AIDS 9, 822-823 (1995).
20. Van't Wout, A. et al. Macrophage-tropic variants initiate human immunodeficiency virus type-1 infection after sexual, parenteral and vertical transmission. J. Clin. Invest. 94, 2060-2067 (1994).
21. Tatt, I. D., Barlow, K. L., Nicoll, A. & Clewley, J. P. The public health significance of HIV-1 subtypes. AIDS 15, S59-S71 (2001).
22. Morris, L. & Williamson, C. Host and viral factors that impact on HIV-1 transmission and disease progression in South Africa. S. Afr. Med. J. 91, 212-215 (2001).
23. Shattock, R. J., Griffin, G. E. & Gorodeski, G. I. In vitro models of mucosal HIV transmission. Nature Med. 6, 607-608 (2000).
24. King, B. F. The permeability of nonhuman primate vaginal epithelium: a freeze-fracture and tracer-perfusion study. J. Ultrastruct. Res. 83, 99-110 (1983).
25. Robboy, S. J., Prade, M. & Cunha, G. in Histology for Pathologists (ed. Sternberg, S. S.) 881-892 (Raven Press, 40. New York, 1992).
26. Smith, S. M., Baskin, G. B. & Marx, P. A. Estrogen protects against vaginal simian immunodeficiency virus. J. Infect. Dis. 182, 708-715 (2000).
27. Marx, P. A. et al. Progesterone implants vaginal transmission and early virus load. Nature Med. 2, 1084-1089 (1996).
28. Dezzutti, C. S. et al. Cervical and prostate primary epithelial cells are not productively infected but sequester human immunodeficiency virus type 1. J. Infect. Dis. 183, 1204-1213 (2001).
29. Novell, M. K., Benrudi, G. I. & Thompson, R. J. Investigation of microtrauma after sexual intercourse. J. Reprod. Med. 29, 269-271 (1984).
30. Cold, C. J. & Taylor, J. R. The prepuce. BJU Int. 83, S34-S44 (1999).
31. Van Howe, R. S. Does circumcision influence sexually transmitted diseases?: a literature review. BJU Int. 83, S52-S62 (1999).
32. Strathdee, S. A., Hogg, R. S., O'Shaughnessy, M. V., Montaner, J. S. & Schechter, M. T. A decade of research on the natural history of HIV infection: Part 2. Cofactors. Clin. Invest. Med. 19, 121-130 (1996).
33. Baeten, J. M. et al. Selenium deficiency is associated with shedding of HIV-1-infected cells in the female genital tract. J. Acquir. Immune Defic. Syndr. 26, 360-364 (2001).
34. Mostad, S. B. et al. Hormonal contraception, vitamin A deficiency, and other risk factors for shedding of HIV-1 infected cells from the cervix and vagina. Lancet 350, 922-927 (1997).
35. Greenhead, P. et al. Parameters of human immunodeficiency virus infection of human cervical tissue and inhibition by vaginal virucides. J. Virol. 74, 5577-5586 (2000).
36. Coombs, R. W., Reichelderfer, P S. & Landay, A. L. Recent observations on HIV type-1 infection in the genital tract of men and women. AIDS 17, 455-480 (2003).
37. Moriyama, A. et al. Secretory leukocyte protease inhibitor (SLPI) concentrations in cervical mucus of women with normal menstrual cycle. Mol. Hum. Reprod. 5, 656-661 (1999).
38. Agace, W. W. et al. Constitutive expression of stromal derived factor-1 by mucosal epithelia and its role in HIV transmission and propagation. Curr. Biol. 10, 325-328 (2000).
39. Amerongen, H. M. et al. Transepithelial transport of HIV-1 by intestinal M cells: a mechanism for transmission of AIDS. J. Acquir. Immune Defic. Syndr. 4, 760-765 (1991).
40. Neutra, M. R. Interaction of viruses and microparticles with apical membranes of M cells: implications for human immunodeficiency virus transmission. J. Infect. Dis. 179, S441-S443 (1999).
41. Bomsel, M. Trancytosis of infectious human immunodeficiency virus across a tight human epithelial cell line barrier. Nature Med. 3, 42-47 (1997).
42. Phillips, D. M. The role of cell-to-cell transmission in HIV infection. AIDS 8, 719-731 (1994).
43. Chenine, A. et al. Primary intestinal epithelial cells can be infected with laboratory-adapted strain HIV type 1 NDK but not with clinical primary isolates. AIDS Res. Hum. Retroviruses 14, 1235-1238 (1998).
44. Delezay, O. et al. Co-expression of CXCR4/fusin and galactosylceramide in the human intestinal epithelial cell line HT-29. AIDS 11, 1311-1318 (1997).
45. Khanna, K. V. et al. Vaginal transmission of cell-associated HIV-1 in the mouse is blocked by a topical, membrane-modifying agent. J. Clin. Invest. 109, 205-211 (2002).
46. Romani, N. et al. Migration of dendritic cells into lymphatics — the Langerhans cell example: routes, regulation and relevance. Int. Rev. Cytol. 207, 237-270 (2001).
47. Zaitseva, M. et al. Expression and function of CCR5 and CXCR4 on human Langerhans cells and macrophages: implications for HIV primary infection. Nature. Med. 12, 1369-1375 (1997).
48. Kawamura, T et al. Candidate microbicides block HIV-1 infection of human immature Langerhans cells within epithelial tissue explants. J. Exp. Med. 192, 1491-1500 (2000).
49. Patterson, B. K. et al. Repertoire of chemokine receptor expression in the female genital tract: implications for human immunodeficiency virus transmission. Am. J. Pathol. 153, 481-490 (1998).
50. + T cells express high levels of CCR5 and are rapidly depleted in simian immunodeficiency virus infection. J. Infect. Dis. 187, 769-776 (2003).
51. Stone, A. Microbicides: a new approach to preventing HIV and other sexually transmitted infections. Nature Rev. Drug Discov. 1, 977-985 (2002).
52. Turpin, J.A. Considerations and development of topical microbicides to inhibit the sexual transmission of HIV. Expert Opin. Investig. Drugs. 11, 1077-1097 (2002).
53. Bourinbaiar, A. S. & Lee-Huang, S. L. Comparative in vitro study of contraceptive agents with anti-HIV activity: Gramicidin, nonoxynol-9, and gossypol. Contraception 49, 131-137 (1994).
54. Van Damme, L. et al. COL-1492 Study Group. Effectiveness of COL-1492, a nonoxynol-9 vaginal gel, on HIV-1 transmission in female sex workers: a randomised controlled trial. Lancet 360, 971-977 (2002).
55. Poignard, P., Ollman Saphire, E., Parren, P. W. H. I. & Burton, D. R. Gp120: Biologic aspects of structural features. Annu. Rev. Immunol. 19, 253-274 (2001).
56. Bugelski, P J., Ellens, H., Hart, T. K. & Kirsh, R. L. Soluble CD4 and dextran sulphate mediate release of gp120 from HIV-1: Implications for clinical trials. J. Acquir. Immune Defic. Syndr. 4, 923-924 (1991).
57. Neurath, A. R., Strick, N., Jiang, S., Li, Y. Y. & Debnath, A. K. Anti-HIV-1 activity of cellulose acetate phthalate: Synergy with soluble CD4 and induction of 'dead end' gp41 six-helix bundles. BMC Infect. Dis. 2, 6 (2002).
58. Walker, B. D. & Korber, B. T. Immune control of HIV: the obstacles of HLA and viral diversity. Nature Immunol. 2, 473-475 (2001).
59. Doms, R. W. Beyond receptor expression: The influence of receptor conformation, density, and affinity in HIV-1 infection. Virology 276, 229-237 (2000).
60. Reeves, J. D. et al. Sensitivity of HIV-1 to entry inhibitors correlates with envelope/coreceptor affinity, receptor density, and fusion kinetics. Proc. Natl Acad. Sci. USA 99, 16249-16254 (2002).
61. Trkola, A. et al. Cross-clade neutralization of primary isolates of human immunodeficiency virus type 1 by human monoclonal antibodies and tetrameric CD4 IgG. J. Virol. 69, 6609-6617 (1995).
62. Parren, P. W. H. I. & Burton, D. R. The antiviral activity of antibodies in vitro and in vivo. Adv. Immunol. 77, 195-262 (2001).
63. Zwick, M. B. et al. Neutralization synergy of human immunodeficiency virus type 1 primary isolates by cocktails of broadly neutralizing antibodies. J. Virol. 75, 12198-12208 (2001).
64. O'Hara, B. M. & Olson, W. C. HIV entry inhibitors in clinical development. Curr. Opin. Pharmacol. 2, 523-528 (2002).
65. Scanlan, C. N. et al. The broadly neutralizing anti-human immunodeficiency virus type 1 antibody 2G12 recognizes a cluster of α1→2 mannose residues on the outer face of gp120. J. Virol. 76, 7306-7321 (2002).
66. Sanders, R. W. et al. The mannose-dependent epitope for neutralizing antibody 2G12 on human immunodeficiency virus type 1 glycoprotein gp120. J. Virol. 76, 7293-7305 (2002).
67. Trkola, A. et al. CD4-dependent, antibody-sensitive interactions between HIV-1 and its co-receptor CCR-5. Nature 384, 184-187 (1996).
68. Kilby, J. M. et al. Potent suppression of HIV-1 replication in humans by T-20, a peptide inhibitor of gp41-mediated virus entry. Nature Med. 4, 1302-1307 (1998).
69. Baldwin, C. E., Sanders, R. W. & Berkhout, B. Inhibiting HIV-1 entry with fusion inhibitors. Curr. Med. Chem. 10, 1773-1782 (2003).
70. Melikyan, G. B. et al. Evidence that the transition of HIV-1 gp41 into a six-helix bundle, not the bundle configuration, induces membrane fusion. J. Cell Biol. 151, 413-423 (2000).
71. Gallo, S. A., Puri, A. & Blumenthal, R. HIV-1 gp41 six-helix bundle formation occurs rapidly after the engagement of gp120 by CXCR4 in the HIV-1 Env-mediated fusion process. Biochemistry 40, 12231-12236 (2001).
72. Root, M. J. & Hamer, D. H. Targeting therapeutics to an exposed and conserved binding element of the HIV-1 fusion protein. Proc. Natl Acad. Sci. USA 100, 5016-5023 (2003).
73. Moulard, M. et al. Selective interactions of polyanions with basic surfaces on human immunodeficiency virus type 1 gp120. J. Virol. 74, 1948-1960 (2000).
74. Shattock, R. J. & Doms, R. W. AIDS models: Microbicides could learn from vaccines. Nature Med. 8, 425 (2002).
75. Kwong, P., Wyatt, R., Sattentau, Q. J., Sodroski, J. & Hendrickson, W. A. Oligomeric modeling and electrostatic analysis of the gp120 envelope glycoprotein of human immunodeficiency virus. J. Virol. 74, 1961-1972 (2000).
76. Bewley, C. A. Solution structure of a cyanovirin-N:Manα1-2Manα complex: Structural basis for high-affinity carbohydrate-mediated binding to gp120. Structure 9, 31-40 (2001).
77. Dey, B. et al. Multiple antiviral activities of cyanovirin-N: blocking of human immunodeficiency virus type 1 gp120 interaction with CD4 and coreceptor and inhibition of diverse enveloped viruses. J. Virol. 74, 4562-4569 (2000).
78. Pohlmann, S., Baribaud, F. & Doms, R. W. DC-SIGN and DC-SIGNR: helping hands for HIV. Trends Immunol. 22, 643-646 (2001).
79. Baribaud, F., Pohlmann, S. & Doms, R. W. The role of DC-SIGN and DC-SIGNR in HIV and SIV attachment, infection, and transmission. Virology 286, 1-6 (2001).
80. Kwon, D. S., Gregorio, G., Bitton, N., Hendrickson, W. A. & Littman, D. R. DC-SIGN mediated internalization of HIV is required for trans-enhancement of T cell infection. Immunity 16, 135-144 (2002).
81. Jameson, B. et al. Expression of DC-SIGN by dendritic cells of intestinal and genital mucosae in humans and rhesus macaques. J. Virol. 76, 1866-1875 (2002).
82. Baribaud, F., Doms, R. W. & Pohlmann, S. The role of DC-SIGN and DC-SIGNR in HIV and Ebola virus infection: can potential therapeutics block virus transmission and dissemination? Expert Opin. Ther. Targets 6, 1-9 (2002).
83. Turville, S.G. et al. Diversity of receptors binding HIV on dendritic cell subsets. Nature Immunol. 3, 975-983 (2002).
84. Hong, P W. et al. Human immunodeficiency virus envelope (gp120) binding to DC-SIGN and primary dendritic cells is carbohydrate dependent but does not involve 2G12 or cyanovirin binding sites: Implications for structural analyses of gp120-DC SIGN binding. J. Virol. 76, 2855-12865 (2002).
85. Lin, G. et al. Differential N-linked glycosylation of human immunodeficiency virus and Ebola virus envelope glycoproteins modulates interactions with DC-SIGN and DC-SIGNR. J. Virol. 77, 1337-1346 (2003).
86. Moore, J. P & Sweet, R. W. The HIV gp120-CD4 interaction: A target for pharmacological or immunological intervention? Perspect. Drug Discov. Design 1, 235-250 (1993).
87. Sattentau, Q. J. & Weiss, R. A. The CD4 antigen: physiological ligand and HIV receptor. Cell 52, 631-632 (1988).
88. + cells from virus binding. J. Exp. Med. 172, 1233-1242 (1990).
89. Burkly, L. C. et al. Inhibition of HIV entry by a CD4 domain 2 specific monoclonal antibody: Dissecting the basis for its inhibitory effect on HIV-induced cell fusion. J. Immunol. 149, 1779-1787 (1992).
90. + cells. J. Virol. 66, 4784-4793 (1992).
91. Reimann, K. A., Khunkhun, R., Lin, W., Gordon, W. & Fung, M. A humanized, nondepleting anti-CD4 antibody that blocks virus entry inhibits virus replication in Rhesus monkeys chronically infected with simian immunodeficiency virus. AIDS Res. Hum. Retrovirus 18, 747-755 (2002).
92. Dragic, T. An overview of the determinants of CCR5 and CXCR4 co receptor function. J. Gen. Virol. 82, 1807-1814 (2001).
93. Pierson, T. C. & Doms, R. W. HIV-1 entry inhibitors: new targets, novel therapies. Immunol. Lett. 85, 113-118 (2003).
94. Moore, J. P. and Stevenson, M. New targets for inhibitors of HIV-1 replication. Nature Rev. Mol. Cell Biol. 1, 40-49 (2000).
95. Wu, L. et al. Interaction of chemokine receptor CCR5 with its ligands: multiple domains for HIV-1 gp120 binding and a single domain for chemokine binding. J. Exp. Med. 186, 1373-1381 (1997).
96. Trkola, A. et al. Potent, broad-spectrum inhibition of human immunodeficiency virus type 1 by the CCR5 monoclonal antibody PRO 140. J. Virol. 75, 579-588 (2001).
97. Simmons, G. et al. Potent inhibition of HIV-1 infectivity in macrophages and lymphocytes by a novel CCR5 antagonist. Science 276, 276-279 (1997).
98. Torre, V. S. et al. Variable sensitivity of CCR5-tropic human immunodeficiency virus type 1 isolates to inhibition by RANTES analogs. J. Virol. 74, 4868-4876 (2000).
99. Rusconi, S. et al. Combination of CCR5 and CXCR4 inhibitors in therapy of human immunodeficiency virus type 1 infection: In vitro studies of mixed virus infections. J. Virol. 74, 9328-9332 (2000).
100. Kawamura, T. et al. R5 HIV productively infects Langerhans cells, and infection levels are regulated by compound CCR5 polymorphisms. Proc. Natl Acad. Sci. USA. 100, 8401-8406 (2003).
101. Kazmierski, W. et al. Recent progress in discovery of small-molecule CCR5 chemokine receptor ligands as HIV-1 inhibitors. Bioorg. Med. Chem. 11, 2663-2676 (2003).
102. Strizki, J. M. et al. SCH-C (SCH 351125), an orally bioavailable small molecule antagonist of the chemokine receptor CCR5 is a potent inhibitor of HIV-1 infection in vitro and in vivo. Proc. Natl Acad. Sci. USA 98, 12718-12723 (2001).
103. Trkola, A. et al. HIV-1 escape from a small molecule, CCR5-specific entry inhibitor does not involve CXCR4 use. Proc. Natl Acad. Sci. USA 99, 395-400 (2002).
104. Donzella, G. A. et al. AMD3100, a small molecule inhibitor of HIV-1 entry via the CXCR4 co-receptor. Nature Med. 4, 72-77 (1998).
105. Sabbe, R. et al. Donor- and ligand-dependent differences in C-C chemokine receptor expression. J. Virol. 75, 661-671 (2001).
106. Nagashima, K. A. et al. Human immunodeficiency virus type 1 entry inhibitors PRO 542 and T 20 are potently synergistic in blocking virus-cell and cell-cell fusion. J. Infect. Dis. 183, 1121-1125 (2001).
107. Tremblay, C. L. et al. Anti-human immunodeficiency virus interactions of SCH-C (SCH 351125), a CCR5 antagonist, with other antiretroviral agents in vitro. Antimicrob. Agents Chemother. 46, 1336-1339 (2002).
108. Veazey, R. S. et al. Prevention of virus transmission to macaque monkeys by a vaginally applied monoclonal antibody to HIV-1 gp120. Nature Med. 9, 343-346 (2003).
109. Gupta, P. et al. High viral load in semen of human immunodeficiency virus type I-infected men at all stages of disease and its reduction by therapy by protease and non- nucleoside reverse transcriptase inhibitors. J. Virol. 31, 6271-6275 (1997).
110. Schillberg, S., Fischer, R. & Emans, N. Molecular farming of recombinant antibodies in plants. Cell Mol. Life Sci. 60, 433-445 (2003).
111. Sherwood, J. K., Zeitlin, L., Whaley, K. J., Cone, R. A. & Saltzman, M. Controlled release of antibodies for long-term topical passive immunoprotection of female mice against genital herpes. Nature Biotechnol. 14, 468-471 (1996).
112. Dean, M. et al. Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Science 273, 1856-1862 (1996).
113. Liu, R. et al. Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection. Cell 86, 367-377 (1996).
114. Berger, E. A., Murphy, P. M. & Farber, J. M. Chemokine receptors as HIV-1 coreceptors: Roles in viral entry, tropism, and disease. Annu. Rev. Immunol. 17, 657-700 (1999).
115. Geijtenbeek, T. B. et al. DC-SIGN, a dendritic cell-specific HIV-1-binding protein that enhances trans-infection of T cells. Cell 100, 587-597 (2000).
116. Pope, M. Mucosal dendritic cells and immunodeficiency viruses. J. Infect. Dis. 179, S427-S430 (1999).
117. King, N. J., Parr, E. L. & Parr, M. B. Migration of lymphoid cells from vaginal epithelium to iliac lymph nodes in relation to vaginal infection by herpes simplex virus type 2. J. Immunol. 160, 1173-1180 (1998).
118. Liao, Z., Roos, J. W. & Hildreth, J. E. Increased infectivity of HIV type 1 particles bound to cell surface and solid-phase ICAM-1 and VCAM-1 through acquired adhesion molecules LFA-1 and VLA-4. AIDS Res. Hum. Retroviruses 16, 355-366 (2000).
119. + target cells is a major mechanism of T cell line-adapted HIV-1 neutralization. J. Exp. Med. 186, 1287-1298 (1997).
120. Layne, S. P., Merges, M. J., Dembo, M. B., Spouge, J. L. & Nara, P. L. HIV requires multiple gp120 molecules for CD4- mediated infection. Nature 346, 277-279 (1990).
121. Kuhmann, S. E., Platt, E. J., Kozak, S. L. & Kabat, D. J. Cooperation of multiple CCR5 coreceptors is required for infections by human immunodeficiency virus type 1. Virology 7, 7005-7015 (2000).
122. Wyatt, R. & Sodroski, J. The HIV-1 envelope glycoproteins: fusogens, antigens, and immunogens. Science 280, 1884-1888 (1998).
123. Chan, D. C., Fass, D., Berger, J. M. & Kim, P S. Core structure of gp41 from the HIV envelope glycoprotein. Cell 89, 263-273 (1997).
124. Doms, R. W. and Moore, J. P. HIV-1 membrane fusion: Targets of opportunity. J. Cell Biol. 151, F9-F14 (2000).
125. Swingler, S. et al. HIV-1 Nef mediates lymphocyte chemotaxis and activation by infected macrophages. Nature Med. 5, 997-103 (1999).
126. Izmailova, E. et al. HIV-1 Tat reprograms immature dendritic cells to express chemoattractants for activated T cells and macrophages. Nature Med. 9, 191-197 (2003).