Conformational masking and receptor-dependent unmasking of highly conserved env epitopes recognized by non-neutralizing antibodies that mediate potent ADCC against HIV-1

Viruses

Volumn 7, Issue 9, 2015, Pages 5115-5132

  Lewis, George K ^a   Finzi, Andrés ^b   De Vico, Anthony L ^a   Pazgier, Marzena ^a  

^a UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE   (United States)

^b CENTRE HOSPITALIER DE L UNIVERSITÉ DE MONTRÉAL   (Canada)

Author keywords

AIDS; Antibody; Effector function; Fc; HIV 1; Protection; Vaccine

Indexed keywords

CD4 ANTIGEN; CHEMOKINE RECEPTOR CCR5; CHEMOKINE RECEPTOR CXCR4; EPITOPE; FC RECEPTOR; GLYCOPROTEIN GP 120; HUMAN IMMUNODEFICIENCY VIRUS VACCINE; MATRIX PROTEIN; NEUTRALIZING ANTIBODY; HUMAN IMMUNODEFICIENCY VIRUS ANTIBODY; VIRUS ENVELOPE PROTEIN;

ANTIBODY DEPENDENT CELLULAR CYTOTOXICITY; ANTIBODY RESPONSE; CLUSTER ANALYSIS; CONFORMATIONAL TRANSITION; CRYOELECTRON MICROSCOPY; CRYSTAL STRUCTURE; FLUORESCENCE RESONANCE ENERGY TRANSFER; HUMAN IMMUNODEFICIENCY VIRUS 1; NONHUMAN; PASSIVE IMMUNIZATION; REVIEW; VIREMIA; VIRUS ENTRY; VIRUS NEUTRALIZATION; VIRUS RELEASE; VIRUS TRANSMISSION; X RAY CRYSTALLOGRAPHY; ANIMAL; CHEMISTRY; HUMAN; IMMUNOLOGY; METABOLISM; PRIMATE; PROTEIN CONFORMATION;

ANIMALS; ANTIBODY-DEPENDENT CELL CYTOTOXICITY; ENV GENE PRODUCTS, HUMAN IMMUNODEFICIENCY VIRUS; EPITOPES; HIV ANTIBODIES; HIV-1; HUMANS; PRIMATES; PROTEIN CONFORMATION;

EID: 84942096625     PISSN: None     EISSN: 19994915     Source Type: Journal    
DOI: 10.3390/v7092856     Document Type: Review

References (148)

1. Emini, E.A.; Nara, P.L.; Schleif, W.A.; Lewis, J.A.; Davide, J.P.; Lee, D.R.; Kessler, J.; Conley, S.; Matsushita, S.; Putney, S.D., et al. Antibody-mediated in vitro neutralization of human immunodeficiency virus type 1 abolishes infectivity for chimpanzees. J. Virol. 1990, 64, 3674–3678. [PubMed]
2. Emini, E.A.; Schleif, W.A.; Nunberg, J.H.; Conley, A.J.; Eda, Y.; Tokiyoshi, S.; Putney, S.D.; Matsushita, S.; Cobb, K.E.; Jett, C.M., et al. Prevention of HIV-1 infection in chimpanzees by gp120 v3 domain-specific monoclonal antibody. Nature 1992, 355, 728–730. [CrossRef][PubMed]
3. Putkonen, P.; Thorstensson, R.; Ghavamzadeh, L.; Albert, J.; Hild, K.; Biberfeld, G.; Norrby, E. Prevention of HIV-2 and sivsm infection by passive immunization in cynomolgus monkeys. Nature 1991, 352, 436–438. [CrossRef][PubMed]
4. Foresman, L.; Jia, F.; Li, Z.; Wang, C.; Stephens, E.B.; Sahni, M.; Narayan, O.; Joag, S.V. Neutralizing antibodies administered before, but not after, virulent shiv prevent infection in macaques. AIDS Res. Hum. Retrovir. 1998, 14, 1035–1043. [CrossRef][PubMed]
5. Baba, T.W.; Liska, V.; Hofmann-Lehmann, R.; Vlasak, J.; Xu, W.; Ayehunie, S.; Cavacini, L.A.; Posner, M.R.; Katinger, H.; Stiegler, G., et al. Human neutralizing monoclonal antibodies of the IgG1 subtype protect against mucosal simian-human immunodeficiency virus infection. Nat. Med. 2000, 6, 200–206. [PubMed]
6. Mascola, J.R.; Stiegler, G.; VanCott, T.C.; Katinger, H.; Carpenter, C.B.; Hanson, C.E.; Beary, H.; Hayes, D.; Frankel, S.S.; Birx, D.L., et al. Protection of macaques against vaginal transmission of a pathogenic HIV-1/siv chimeric virus by passive infusion of neutralizing antibodies. Nat. Med. 2000, 6, 207–210. [CrossRef][PubMed]
7. Parren, P.W.; Marx, P.A.; Hessell, A.J.; Luckay, A.; Harouse, J.; Cheng-Mayer, C.; Moore, J.P.; Burton, D.R. Antibody protects macaques against vaginal challenge with a pathogenic R5 simian/human immunodeficiency virus at serum levels giving complete neutralization in vitro. J. Virol. 2001, 75, 8340–8347. [CrossRef][PubMed]
8. Hessell, A.J.; Hangartner, L.; Hunter, M.; Havenith, C.E.; Beurskens, F.J.; Bakker, J.M.; Lanigan, C.M.; Landucci, G.; Forthal, D.N.; Parren, P.W., et al. Fc receptor but not complement binding is important in antibody protection against HIV. Nature 2007, 449, 101–104. [CrossRef][PubMed]
9. Moldt, B.; Rakasz, E.G.; Schultz, N.; Chan-Hui, P.Y.; Swiderek, K.; Weisgrau, K.L.; Piaskowski, S.M.; Bergman, Z.; Watkins, D.I.; Poignard, P., et al. Highly potent HIV-specific antibody neutralization in vitro translates into effective protection against mucosal shiv challenge in vivo. Proc. Natl. Acad. Sci. USA 2012, 109, 18921–18925. [CrossRef][PubMed]
10. Shingai, M.; Donau, O.K.; Plishka, R.J.; Buckler-White, A.; Mascola, J.R.; Nabel, G.J.; Nason, M.C.; Montefiori, D.; Moldt, B.; Poignard, P., et al. Passive transfer of modest titers of potent and broadly neutralizing anti-HIV monoclonal antibodies block shiv infection in macaques. J. Exp. Med. 2014, 211, 2061–2074. [CrossRef][PubMed]
11. Hessell, A.J.; Poignard, P.; Hunter, M.; Hangartner, L.; Tehrani, D.M.; Bleeker, W.K.; Parren, P.W.; Marx, P.A.; Burton, D.R. Effective, low-titer antibody protection against low-dose repeated mucosal shiv challenge in macaques. Nat. Med. 2009, 15, 951–954. [CrossRef][PubMed]
12. Hessell, A.J.; Rakasz, E.G.; Poignard, P.; Hangartner, L.; Landucci, G.; Forthal, D.N.; Koff, W.C.; Watkins, D.I.; Burton, D.R. Broadly neutralizing human anti-HIV antibody 2g12 is effective in protection against mucosal shiv challenge even at low serum neutralizing titers. PLoS Pathog. 2009, 5, e1000433. [CrossRef][PubMed]
13. Hessell, A.J.; Rakasz, E.G.; Tehrani, D.M.; Huber, M.; Weisgrau, K.L.; Landucci, G.; Forthal, D.N.; Koff, W.C.; Poignard, P.; Watkins, D.I., et al. Broadly neutralizing monoclonal antibodies 2f5 and 4e10 directed against the human immunodeficiency virus type 1 gp41 membrane-proximal external region protect against mucosal challenge by simian-human immunodeficiency virus shivba-l. J. Virol. 2010, 84, 1302–1313. [CrossRef][PubMed]
14. Burton, D.R.; Hessell, A.J.; Keele, B.F.; Klasse, P.J.; Ketas, T.A.; Moldt, B.; Dunlop, D.C.; Poignard, P.; Doyle, L.A.; Cavacini, L., et al. Limited or no protection by weakly or nonneutralizing antibodies against vaginal shiv challenge of macaques compared with a strongly neutralizing antibody. Proc. Natl. Acad. Sci. USA 2011, 108, 11181–11186. [CrossRef][PubMed]
15. Shibata, R.; Igarashi, T.; Haigwood, N.; Buckler-White, A.; Ogert, R.; Ross, W.; Willey, R.; Cho, M.W.; Martin, M.A. Neutralizing antibody directed against the HIV-1 envelope glycoprotein can completely block HIV-1/siv chimeric virus infections of macaque monkeys. Nat. Med. 1999, 5, 204–210. [CrossRef][PubMed]
16. Walker, L.M.; Phogat, S.K.; Chan-Hui, P.Y.; Wagner, D.; Phung, P.; Goss, J.L.; Wrin, T.; Simek, M.D.; Fling, S.; Mitcham, J.L., et al. Broad and potent neutralizing antibodies from an african donor reveal a new HIV-1 vaccine target. Science 2009, 326, 285–289. [CrossRef][PubMed]
17. Walker, L.M.; Simek, M.D.; Priddy, F.; Gach, J.S.; Wagner, D.; Zwick, M.B.; Phogat, S.K.; Poignard, P.; Burton, D.R. A limited number of antibody specificities mediate broad and potent serum neutralization in selected HIV-1 infected individuals. PLoS Pathog. 2010, 6, e1001028. [CrossRef][PubMed]
18. Burton, D.R.; Mascola, J.R. Antibody responses to envelope glycoproteins in HIV-1 infection. Nat. Immunol. 2015, 16, 571–576. [CrossRef][PubMed]
19. Lewis, G.K. Honing a harder-hitting hammerhead improves broadly neutralizing antibody breadth and potency. J. Clin. Investig. 2015, 125, 1–4. [CrossRef][PubMed]
20. Klein, F.; Diskin, R.; Scheid, J.F.; Gaebler, C.; Mouquet, H.; Georgiev, I.S.; Pancera, M.; Zhou, T.; Incesu, R.B.; Fu, B.Z., et al. Somatic mutations of the immunoglobulin framework are generally required for broad and potent HIV-1 neutralization. Cell 2013, 153, 126–138. [CrossRef][PubMed]
21. Lewis, G.K.; DeVico, A.L.; Gallo, R.C. Antibody persistence and t-cell balance: Two key factors confronting HIV vaccine development. Proc. Natl. Acad. Sci. USA 2014, 111, 15614–15621. [CrossRef][PubMed]
22. Moog, C.; Dereuddre-Bosquet, N.; Teillaud, J.L.; Biedma, M.E.; Holl, V.; van Ham, G.; Heyndrickx, L.; van Dorsselaer, A.; Katinger, D.; Vcelar, B., et al. Protective effect of vaginal application of neutralizing and nonneutralizing inhibitory antibodies against vaginal shiv challenge in macaques. Mucosal Immunol. 2014, 7, 46–56. [CrossRef][PubMed]
23. Dugast, A.S.; Chan, Y.; Hoffner, M.; Licht, A.; Nkolola, J.; Li, H.; Streeck, H.; Suscovich, T.J.; Ghebremichael, M.; Ackerman, M.E., et al. Lack of protection following passive transfer of polyclonal highly functional low-dose non-neutralizing antibodies. PLoS ONE 2014, 9, e97229. [CrossRef][PubMed]
24. Van Rompay, K.K.; Berardi, C.J.; Dillard_Telm, S.; Tarara, R.P.; Canfield, D.R.; Valverde, C.R.; Montefiori, D.C.; Cole, K.S.; Montelaro, R.C.; Miller, C.J. Passive immunization of newborn rhesus macaques prevents oral simian immunodeficiency virus infection. J. Infect. Dis. 1998, 177, 1247–1259. [CrossRef][PubMed]
25. Forthal, D.N.; Landucci, G.; Cole, K.S.; Marthas, M.; Becerra, J.C.; van Rompay, K. Rhesus macaque polyclonal and monoclonal antibodies inhibit simian immunodeficiency virus in the presence of human or autologous rhesus effector cells. J. Virol. 2006, 80, 9217–9225. [CrossRef][PubMed]
26. Florese, R.H.; Van Rompay, K.K.; Aldrich, K.; Forthal, D.N.; Landucci, G.; Mahalanabis, M.; Haigwood, N.; Venzon, D.; Kalyanaraman, V.S.; Marthas, M.L., et al. Evaluation of passively transferred, nonneutralizing antibody-dependent cellular cytotoxicity-mediating IgG in protection of neonatal rhesus macaques against oral sivmac251 challenge. J. Immunol. 2006, 177, 4028–4036. [CrossRef][PubMed]
27. Lewis, G.K. Qualitative and quantitative variables that affect the potency of Fc-mediated effector function in vitro and in vivo: Considerations for passive immunization using non-neutralizing antibodies. Curr. HIV Res. 2013, 11, 354–364. [CrossRef][PubMed]
28. Lewis, G.K. Role of Fc-mediated antibody function in protective immunity against HIV-1. Immunology 2014, 142, 46–57. [CrossRef][PubMed]
29. Lewis, G.K.; Guan, Y.; Kamin-Lewis, R.; Sajadi, M.; Pazgier, M.; Devico, A.L. Epitope target structures of Fc-mediated effector function during HIV-1 acquisition. Curr. Opin. HIV AIDS 2014, 9, 263–270. [CrossRef][PubMed]
30. Forthal, D.; Hope, T.J.; Alter, G. New paradigms for functional HIV-specific nonneutralizing antibodies. Curr. Opin. HIV AIDS 2013, 8, 392–400. [CrossRef][PubMed]
31. Ackerman, M.E.; Dugast, A.S.; Alter, G. Emerging concepts on the role of innate immunity in the prevention and control of HIV infection. Ann. Rev. Med. 2012, 63, 113–130. [CrossRef][PubMed]
32. Pancera, M.; Zhou, T.; Druz, A.; Georgiev, I.S.; Soto, C.; Gorman, J.; Huang, J.; Acharya, P.; Chuang, G.Y.; Ofek, G., et al. Structure and immune recognition of trimeric pre-fusion HIV-1 env. Nature 2014, 514, 455–461. [CrossRef][PubMed]
33. Julien, J.P.; Cupo, A.; Sok, D.; Stanfield, R.L.; Lyumkis, D.; Deller, M.C.; Klasse, P.J.; Burton, D.R.; Sanders, R.W.; Moore, J.P., et al. Crystal structure of a soluble cleaved HIV-1 envelope trimer. Science 2013, 342, 1477–1483. [CrossRef][PubMed]
34. Lyumkis, D.; Julien, J.P.; de Val, N.; Cupo, A.; Potter, C.S.; Klasse, P.J.; Burton, D.R.; Sanders, R.W.; Moore, J.P.; Carragher, B., et al. Cryo-em structure of a fully glycosylated soluble cleaved HIV-1 envelope trimer. Science 2013, 342, 1484–1490. [CrossRef][PubMed]
35. Munro, J.B.; Gorman, J.; Ma, X.; Zhou, Z.; Arthos, J.; Burton, D.R.; Koff, W.C.; Courter, J.R.; Smith, A.B., III; Kwong, P.D., et al. Conformational dynamics of single HIV-1 envelope trimers on the surface of native virions. Science 2014, 346, 759–763. [CrossRef][PubMed]
36. Joyner, A.S.; Willis, J.R.; Crowe, J.E., Jr.; Aiken, C. Maturation-induced cloaking of neutralization epitopes on HIV-1 particles. PLoS Pathog. 2011, 7, e1002234. [CrossRef][PubMed]
37. Dimitrov, A.S.; Jacobs, A.; Finnegan, C.M.; Stiegler, G.; Katinger, H.; Blumenthal, R. Exposure of the membrane-proximal external region of HIV-1 gp41 in the course of HIV-1 envelope glycoprotein-mediated fusion. Biochemistry 2007, 46, 1398–1401. [CrossRef][PubMed]
38. Finnegan, C.M.; Berg, W.; Lewis, G.K.; DeVico, A.L. Antigenic properties of the human immunodeficiency virus transmembrane glycoprotein during cell-cell fusion. J. Virol. 2002, 76, 12123–12134. [CrossRef][PubMed]
39. Kong, L.; Lee, J.H.; Doores, K.J.; Murin, C.D.; Julien, J.P.; McBride, R.; Liu, Y.; Marozsan, A.; Cupo, A.; Klasse, P.J., et al. Supersite of immune vulnerability on the glycosylated face of HIV-1 envelope glycoprotein gp120. Nat. Struct. Mol. Biol. 2013, 20, 796–803. [CrossRef][PubMed]
40. Corti, D.; Lanzavecchia, A. Broadly neutralizing antiviral antibodies. Ann. Rev. Immunol. 2013, 31, 705–742. [CrossRef][PubMed]
41. Sievers, S.A.; Scharf, L.; West, A.P., Jr.; Bjorkman, P.J. Antibody engineering for increased potency, breadth and half-life. Curr. Opin. HIV AIDS 2015, 10, 151–159. [CrossRef][PubMed]
42. Galimidi, R.P.; Klein, J.S.; Politzer, M.S.; Bai, S.; Seaman, M.S.; Nussenzweig, M.C.; West, A.P., Jr.; Bjorkman, P.J. Intra-spike crosslinking overcomes antibody evasion by HIV-1. Cell 2015, 160, 433–446. [CrossRef][PubMed]
43. Guan, Y.; Pazgier, M.; Sajadi, M.M.; Kamin-Lewis, R.; Al-Darmarki, S.; Flinko, R.; Lovo, E.; Wu, X.; Robinson, J.E.; Seaman, M.S., et al. Diverse specificity and effector function among human antibodies to HIV-1 envelope glycoprotein epitopes exposed by CD4 binding. Proc. Natl. Acad. Sci. USA 2013, 110, E69–E78. [CrossRef][PubMed]
44. Veillette, M.; Desormeaux, A.; Medjahed, H.; Gharsallah, N.E.; Coutu, M.; Baalwa, J.; Guan, Y.; Lewis, G.; Ferrari, G.; Hahn, B.H., et al. Interaction with cellular CD4 exposes HIV-1 envelope epitopes targeted by antibody-dependent cell-mediated cytotoxicity. J. Virol. 2014, 88, 2633–2644. [CrossRef][PubMed]
45. Ferrari, G.; Pollara, J.; Kozink, D.; Harms, T.; Drinker, M.; Freel, S.; Moody, M.A.; Alam, S.M.; Tomaras, G.D.; Ochsenbauer, C., et al. An HIV-1 gp120 envelope human monoclonal antibody that recognizes a C1 conformational epitope mediates potent antibody-dependent cellular cytotoxicity (adcc) activity and defines a common adcc epitope in human HIV-1 serum. J. Virol. 2011, 85, 7029–7036. [CrossRef][PubMed]
46. Wilen, C.B.; Tilton, J.C.; Doms, R.W. Molecular mechanisms of HIV entry. Adv. Exp. Med. Biol. 2012, 726, 223–242. [PubMed]
47. Wilen, C.B.; Tilton, J.C.; Doms, R.W. HIV: Cell binding and entry. Cold Spring Harb. Perspect. Med. 2012, 2. [CrossRef][PubMed]
48. Blumenthal, R.; Durell, S.; Viard, M. HIV entry and envelope glycoprotein-mediated fusion. J. Biol. Chem. 2012, 287, 40841–40849. [CrossRef][PubMed]
49. Guttman, M.; Cupo, A.; Julien, J.P.; Sanders, R.W.; Wilson, I.A.; Moore, J.P.; Lee, K.K. Antibody potency relates to the ability to recognize the closed, pre-fusion form of HIV Env. Nat. Commun. 2015, 6, 6144. [CrossRef][PubMed]
50. DeVico, A.L. CD4-induced epitopes in the HIV envelope glycoprotein, gp120. Curr. HIV Res. 2007, 5, 561–571. [CrossRef][PubMed]
51. Guttman, M.; Garcia, N.K.; Cupo, A.; Matsui, T.; Julien, J.P.; Sanders, R.W.; Wilson, I.A.; Moore, J.P.; Lee, K.K. CD4-induced activation in a soluble HIV-1 Env trimer. Structure 2014, 22, 974–984. [CrossRef][PubMed]
52. Sundquist, W.I.; Krausslich, H.G. HIV-1 assembly, budding, and maturation. Cold Spring Harb. Perspect. Med. 2012, 2. [CrossRef]
53. Jiang, J.; Aiken, C. Maturation-dependent human immunodeficiency virus type 1 particle fusion requires a carboxyl-terminal region of the gp41 cytoplasmic tail. J. Virol. 2007, 81, 9999–10008. [CrossRef][PubMed]
54. Jiang, J.; Aiken, C. Maturation of the viral core enhances the fusion of HIV-1 particles with primary human t cells and monocyte-derived macrophages. Virology 2006, 346, 460–468. [CrossRef][PubMed]
55. Wyma, D.J.; Kotov, A.; Aiken, C. Evidence for a stable interaction of gp41 with pr55(gag) in immature human immunodeficiency virus type 1 particles. J. Virol. 2000, 74, 9381–9387. [CrossRef][PubMed]
56. Murakami, T.; Ablan, S.; Freed, E.O.; Tanaka, Y. Regulation of human immunodeficiency virus type 1 Env-mediated membrane fusion by viral protease activity. J. Virol. 2004, 78, 1026–1031. [CrossRef][PubMed]
57. Blumberg, R.S.; Paradis, T.; Hartshorn, K.L.; Vogt, M.; Ho, D.D.; Hirsch, M.S.; Leban, J.; Sato, V.L.; Schooley, R.T. Antibody-dependent cell-mediated cytotoxicity against cells infected with the human immunodeficiency virus. J. Infect. Dis. 1987, 156, 878–884. [CrossRef][PubMed]
58. Lyerly, H.K.; Matthews, T.J.; Langlois, A.J.; Bolognesi, D.P.; Weinhold, K.J. Human T-cell lymphotropic virus IIIB glycoprotein (gp120) bound to CD4 determinants on normal lymphocytes and expressed by infected cells serves as target for immune attack. Proc. Natl. Acad. Sci. USA 1987, 84, 4601–4605. [CrossRef][PubMed]
59. Lyerly, H.K.; Reed, D.L.; Matthews, T.J.; Langlois, A.J.; Ahearne, P.A.; Petteway, S.R., Jr.; Weinhold, K.J. Anti-gp 120 antibodies from HIV seropositive individuals mediate broadly reactive anti-HIV ADCC. AIDS Res. Hum. Retrovir. 1987, 3, 409–422. [CrossRef][PubMed]
60. Rook, A.H.; Lane, H.C.; Folks, T.; McCoy, S.; Alter, H.; Fauci, A.S. Sera from HTLV-III/LAV antibody-positive individuals mediate antibody-dependent cellular cytotoxicity against HTLV-III/LAV-infected T cells. J. Immunol. 1987, 138, 1064–1067. [PubMed]
61. Tyler, D.S.; Stanley, S.D.; Zolla-Pazner, S.; Gorny, M.K.; Shadduck, P.P.; Langlois, A.J.; Matthews, T.J.; Bolognesi, D.P.; Palker, T.J.; Weinhold, K.J. Identification of sites within gp41 that serve as targets for antibody-dependent cellular cytotoxicity by using human monoclonal antibodies. J. Immunol. 1990, 145, 3276–3282. [PubMed]
62. Finnegan, C.M.; Berg, W.; Lewis, G.K.; DeVico, A.L. Antigenic properties of the human immunodeficiency virus envelope during cell-cell fusion. J. Virol. 2001, 75, 11096–11105. [CrossRef][PubMed]
63. Mengistu, M.; Ray, K.; Lewis, G.K.; DeVico, A.L. Antigenic properties of the human immunodeficiency virus envelope glycoprotein gp120 on virions bound to target cells. PLoS Pathog. 2015, 11, e1004772. [CrossRef][PubMed]
64. Haynes, B.F.; Gilbert, P.B.; McElrath, M.J.; Zolla-Pazner, S.; Tomaras, G.D.; Alam, S.M.; Evans, D.T.; Montefiori, D.C.; Karnasuta, C.; Sutthent, R., et al. Immune-correlates analysis of an HIV-1 vaccine efficacy trial. N. Engl. J. Med. 2012, 366, 1275–1286. [CrossRef][PubMed]
65. Bonsignori, M.; Pollara, J.; Moody, M.A.; Alpert, M.D.; Chen, X.; Hwang, K.K.; Gilbert, P.B.; Huang, Y.; Gurley, T.C.; Kozink, D.M., et al. Antibody-dependent cellular cytotoxicity-mediating antibodies from an HIV-1 vaccine efficacy trial target multiple epitopes and preferentially use the VH1 gene family. J. Virol. 2012, 86, 11521–11532. [CrossRef][PubMed]
66. DeVico, A.; Fouts, T.; Lewis, G.K.; Gallo, R.C.; Godfrey, K.; Charurat, M.; Harris, I.; Galmin, L.; Pal, R. Antibodies to CD4-induced sites in HIV gp120 correlate with the control of shiv challenge in macaques vaccinated with subunit immunogens. Proc. Natl. Acad. Sci. USA 2007, 104, 17477–17482. [CrossRef][PubMed]
67. Fouts, T.R.; Bagley, K.; Prado, I.J.; Bobb, K.L.; Schwartz, J.A.; Xu, R.; Zagursky, R.J.; Egan, M.A.; Eldridge, J.H.; LaBranche, C.C., et al. Balance of cellular and humoral immunity determines the level of protection by HIV vaccines in rhesus macaque models of HIV infection. Proc. Natl. Acad. Sci. USA 2015, 112, E992–E999. [CrossRef][PubMed]
68. Thomas, M.A.; Tuero, I.; Demberg, T.; Vargas-Inchaustegui, D.A.; Musich, T.; Xiao, P.; Venzon, D.; LaBranche, C.; Montefiori, D.C.; DiPasquale, J., et al. HIV-1 CD4-induced (CD4i) gp120 epitope vaccines promote b and t-cell responses that contribute to reduced viral loads in rhesus macaques. Virology 2014, 471–473, 81–92. [CrossRef][PubMed]
69. Barouch, D.H.; Alter, G.; Broge, T.; Linde, C.; Ackerman, M.E.; Brown, E.P.; Borducchi, E.N.; Smith, K.M.; Nkolola, J.P.; Liu, J., et al. HIV-1 vaccines. Protective efficacy of adenovirus/protein vaccines against siv challenges in rhesus monkeys. Science 2015, 349, 320–324. [CrossRef][PubMed]
70. Wren, L.H.; Chung, A.W.; Isitman, G.; Kelleher, A.D.; Parsons, M.S.; Amin, J.; Cooper, D.A.; Stratov, I.; Navis, M.; Kent, S.J. Specific antibody-dependent cellular cytotoxicity responses associated with slow progression of HIV infection. Immunology 2013, 138, 116–123. [CrossRef][PubMed]
71. Lambotte, O.; Pollara, J.; Boufassa, F.; Moog, C.; Venet, A.; Haynes, B.F.; Delfraissy, J.F.; Saez-Cirion, A.; Ferrari, G. High antibody-dependent cellular cytotoxicity responses are correlated with strong cd8 t cell viral suppressive activity but not with b57 status in HIV-1 elite controllers. PLoS ONE 2013, 8, e74855. [CrossRef][PubMed]
72. Johansson, S.E.; Rollman, E.; Chung, A.W.; Center, R.J.; Hejdeman, B.; Stratov, I.; Hinkula, J.; Wahren, B.; Karre, K.; Kent, S.J., et al. Nk cell function and antibodies mediating adcc in HIV-1-infected viremic and controller patients. Viral Immunol. 2011, 24, 359–368. [CrossRef][PubMed]
73. Chung, A.W.; Navis, M.; Isitman, G.; Wren, L.; Silvers, J.; Amin, J.; Kent, S.J.; Stratov, I. Activation of NK cells by adcc antibodies and HIV disease progression. J. Acquir. Immune Defic. Syndr. 2011, 58, 127–131. [CrossRef][PubMed]
74. Chung, A.W.; Navis, M.; Isitman, G.; Centre R.; Finlayson, R.; Bloch, M.; Gelgor, L.; Kelleher, A.; Kent, S.J.; Stratov, I. Activation of nk cells by adcc responses during early HIV infection. Viral Immunol. 2011, 24, 171–175. [CrossRef][PubMed]
75. Chung, A.W.; Isitman, G.; Navis, M.; Kramski, M.; Center, R.J.; Kent, S.J.; Stratov, I. Immune escape from HIV-specific antibody-dependent cellular cytotoxicity (ADCC) pressure. Proc. Natl. Acad. Sci. USA 2011, 108, 7505–7510. [CrossRef][PubMed]
76. Alter, G.; Teigen, N.; Davis, B.T.; Addo, M.M.; Suscovich, T.J.; Waring, M.T.; Streeck, H.; Johnston, M.N.; Staller, K.D.; Zaman, M.T., et al. Sequential deregulation of nk cell subset distribution and function starting in acute HIV-1 infection. Blood 2005, 106, 3366–3369. [CrossRef][PubMed]
77. Nag, P.; Kim, J.; Sapiega, V.; Landay, A.L.; Bremer, J.W.; Mestecky, J.; Reichelderfer, P.; Kovacs, A.; Cohn, J.; Weiser, B., et al. Women with cervicovaginal antibody-dependent cell-mediated cytotoxicity have lower genital HIV-1 RNA loads. J. Infect. Dis. 2004, 190, 1970–1978. [CrossRef][PubMed]
78. Forthal, D.N.; Landucci, G.; Keenan, B. Relationship between antibody-dependent cellular cytotoxicity, plasma HIV type 1 RNA, and CD4+ lymphocyte count. AIDS Res. Hum. Retrovir. 2001, 17, 553–561. [CrossRef][PubMed]
79. Ahmad, R.; Sindhu, S.T.; Toma, E.; Morisset, R.; Vincelette, J.; Menezes, J.; Ahmad, A. Evidence for a correlation between antibody-dependent cellular cytotoxicity-mediating anti-HIV-1 antibodies and prognostic predictors of HIV infection. J. Clin. Immunol. 2001, 21, 227–233. [CrossRef][PubMed]
80. Tranchat, C.; Van de Perre, P.; Simonon-Sorel, A.; Karita, E.; Benchaib, M.; Lepage, P.; Desgranges, C.; Boyer, V.; Trepo, C. Maternal humoral factors associated with perinatal human immunodeficiency virus type-1 transmission in a cohort from kigali, rwanda, 1988–1994. J. Infect. 1999, 39, 213–220. [CrossRef]
81. Baum, L.L.; Cassutt, K.J.; Knigge, K.; Khattri, R.; Margolick, J.; Rinaldo, C.; Kleeberger, C.A.; Nishanian, P.; Henrard, D.R.; Phair, J. HIV-1 gp120-specific antibody-dependent cell-mediated cytotoxicity correlates with rate of disease progression. J. Immunol. 1996, 157, 2168–2173. [PubMed]
82. Jenkins, M.; Landers, D.; Williams-Herman, D.; Wara, D.; Viscarello, R.R.; Hammill, H.A.; Kline, M.W.; Shearer, W.T.; Charlebois, E.D.; Kohl, S. Association between anti-human immunodeficiency virus type 1 (HIV-1) antibody-dependent cellular cytotoxicity antibody titers at birth and vertical transmission of HIV-1. J. Infect. Dis. 1994, 170, 308–312. [CrossRef][PubMed]
83. Ahmad, A.; Morisset, R.; Thomas, R.; Menezes, J. Evidence for a defect of antibody-dependent cellular cytotoxic (adcc) effector function and anti-HIV gp120/41-specific ADCC-mediating antibody titres in HIV-infected individuals. J. Acquir. Immune Defic. Syndr. 1994, 7, 428–437. [PubMed]
84. Broliden, K.; Sievers, E.; Tovo, P.A.; Moschese, V.; Scarlatti, G.; Broliden, P.A.; Fundaro, C.; Rossi, P. Antibody-dependent cellular cytotoxicity and neutralizing activity in sera of HIV-1-infected mothers and their children. Clin. Exp. Immunol. 1993, 93, 56–64. [CrossRef][PubMed]
85. Sawyer, L.A.; Katzenstein, D.A.; Hendry, R.M.; Boone, E.J.; Vujcic, L.K.; Williams, C.C.; Zeger, S.L.; Saah, A.J.; Rinaldo, C.R., Jr.; Phair, J.P., et al. Possible beneficial effects of neutralizing antibodies and antibody-dependent, cell-mediated cytotoxicity in human immunodeficiency virus infection. AIDS Res. Hum. Retrovir. 1990, 6, 341–356. [CrossRef][PubMed]
86. Ljunggren, K.; Moschese, V.; Broliden, P.A.; Giaquinto, C.; Quinti, I.; Fenyo, E.M.; Wahren, B.; Rossi, P.; Jondal, M. Antibodies mediating cellular cytotoxicity and neutralization correlate with a better clinical stage in children born to human immunodeficiency virus-infected mothers. J. Infect. Dis. 1990, 161, 198–202. [CrossRef][PubMed]
87. Ojo-Amaize, E.; Nishanian, P.G.; Heitjan, D.F.; Rezai, A.; Esmail, I.; Korns, E.; Detels, R.; Fahey, J.; Giorgi, J.V. Serum and effector-cell antibody-dependent cellular cytotoxicity (ADCC) activity remains high during human immunodeficiency virus (HIV) disease progression. J. Clin. Immunol. 1989, 9, 454–461. [CrossRef][PubMed]
88. Goudsmit, J.; Ljunggren, K.; Smit, L.; Jondal, M.; Fenyo, E.M. Biological significance of the antibody response to HIV antigens expressed on the cell surface. Arch. Virol. 1988, 103, 189–206. [CrossRef][PubMed]
89. Ljunggren, K.; Bottiger, B.; Biberfeld, G.; Karlson, A.; Fenyo, E.M.; Jondal, M. Antibody-dependent cellular cytotoxicity-inducing antibodies against human immunodeficiency virus. Presence at different clinical stages. J. Immunol. 1987, 139, 2263–2267. [PubMed]
90. Fouts, T.R.; Tuskan, R.; Godfrey, K.; Reitz, M.; Hone, D.; Lewis, G.K.; DeVico, A.L. Expression and characterization of a single-chain polypeptide analogue of the human immunodeficiency virus type 1 gp120-CD4 receptor complex. J. Virol. 2000, 74, 11427–11436. [CrossRef][PubMed]
91. Gomez-Roman, V.R.; Florese, R.H.; Patterson, L.J.; Peng, B.; Venzon, D.; Aldrich, K.; Robert-Guroff, M. A simplified method for the rapid fluorometric assessment of antibody-dependent cell-mediated cytotoxicity. J. Immunol. Methods 2006, 308, 53–67. [CrossRef][PubMed]
92. Carnathan, D.G.; Wetzel, K.S.; Yu, J.; Lee, S.T.; Johnson, B.A.; Paiardini, M.; Yan, J.; Morrow, M.P.; Sardesai, N.Y.; Weiner, D.B., et al. Activated CD4+CCR5+ T cells in the rectum predict increased siv acquisition in sivgag/tat-vaccinated rhesus macaques. Proc. Natl. Acad. Sci. USA 2015, 112, 518–523. [CrossRef][PubMed]
93. Acharya, P.; Tolbert, W.D.; Gohain, N.; Wu, X.; Yu, L.; Liu, T.; Huang, W.; Huang, C.C.; Kwon, Y.D.; Louder, R.K., et al. Structural definition of an antibody-dependent cellular cytotoxicity response implicated in reduced risk for HIV-1 infection. J. Virol. 2014, 88, 12895–12906. [CrossRef][PubMed]
94. Moore, J.P.; McCutchan, F.E.; Poon, S.W.; Mascola, J.; Liu, J.; Cao, Y.; Ho, D.D. Exploration of antigenic variation in gp120 from clades a through f of human immunodeficiency virus type 1 by using monoclonal antibodies. J. Virol. 1994, 68, 8350–8364. [PubMed]
95. Pancera, M.; Majeed, S.; Ban, Y.E.; Chen, L.; Huang, C.C.; Kong, L.; Kwon, Y.D.; Stuckey, J.; Zhou, T.; Robinson, J.E., et al. Structure of HIV-1 gp120 with gp41-interactive region reveals layered envelope architecture and basis of conformational mobility. Proc. Natl. Acad. Sci. USA 2010, 107, 1166–1171. [CrossRef][PubMed]
96. Finzi, A.; Xiang, S.H.; Pacheco, B.; Wang, L.; Haight, J.; Kassa, A.; Danek, B.; Pancera, M.; Kwong, P.D.; Sodroski, J. Topological layers in the HIV-1 gp120 inner domain regulate gp41 interaction and CD4-triggered conformational transitions. Mol. Cell 2010, 37, 656–667. [CrossRef][PubMed]
97. Pollara, J.; Bonsignori, M.; Moody, M.A.; Liu, P.; Alam, S.M.; Hwang, K.K.; Gurley, T.C.; Kozink, D.M.; Armand, L.C.; Marshall, D.J., et al. HIV-1 vaccine-induced c1 and v2 env-specific antibodies synergize for increased antiviral activities. J. Virol. 2014, 88, 7715–7726. [CrossRef][PubMed]
98. Tomaras, G.D.; Ferrari, G.; Shen, X.; Alam, S.M.; Liao, H.X.; Pollara, J.; Bonsignori, M.; Moody, M.A.; Fong, Y.; Chen, X., et al. Vaccine-induced plasma iga specific for the c1 region of the HIV-1 envelope blocks binding and effector function of IgG. Proc. Natl. Acad. Sci. USA 2013, 110, 9019–9024. [CrossRef][PubMed]
99. Moore, J.P.; Willey, R.L.; Lewis, G.K.; Robinson, J.; Sodroski, J. Immunological evidence for interactions between the first, second, and fifth conserved domains of the gp120 surface glycoprotein of human immunodeficiency virus type 1. J. Virol. 1994, 68, 6836–6847. [PubMed]
100. Koup, R.A.; Robinson, J.E.; Nguyen, Q.V.; Pikora, C.A.; Blais, B.; Roskey, A.; Panicali, D.; Sullivan, J.L. Antibody-dependent cell-mediated cytotoxicity directed by a human monoclonal antibody reactive with gp120 of HIV-1. AIDS 1991, 5, 1309–1314. [CrossRef][PubMed]
101. Alsmadi, O.; Herz, R.; Murphy, E.; Pinter, A.; Tilley, S.A. A novel antibody-dependent cellular cytotoxicity epitope in gp120 is identified by two monoclonal antibodies isolated from a long-term survivor of human immunodeficiency virus type 1 infection. J. Virol. 1997, 71, 925–933. [PubMed]
102. Pollara, J.; Bonsignori, M.; Moody, M.A.; Pazgier, M.; Haynes, B.F.; Ferrari, G. Epitope specificity of human immunodeficiency virus-1 antibody dependent cellular cytotoxicity [adcc] responses. Curr. HIV Res. 2013, 11, 378–387. [CrossRef][PubMed]
103. Santra, S.; Tomaras, G.D.; Warrier, R.; Nicely, N.; Liao, H.X.; Pollara, J.; Liu, P.; Alam, S.M.; Zhang, R.; Cocklin, S., et al. Human non-neutralizing HIV-1 envelope monoclonal antibodies limit the number of founder viruses during shiv mucosal infection in rhesus macaques. PLoS Pathog. 2015, 11. [CrossRef][PubMed]
104. Tudor, D.; Bomsel, M. The broadly neutralizing HIV-1 IgG 2f5 elicits gp41-specific antibody-dependent cell cytotoxicity in a fcgammari-dependent manner. AIDS 2011, 25, 751–759. [CrossRef][PubMed]
105. Hezareh, M.; Hessell, A.J.; Jensen, R.C.; van de Winkel, J.G.; Parren, P.W. Effector function activities of a panel of mutants of a broadly neutralizing antibody against human immunodeficiency virus type 1. J. Virol. 2001, 75, 12161–12168. [CrossRef][PubMed]
106. Moldt, B.; Schultz, N.; Dunlop, D.C.; Alpert, M.D.; Harvey, J.D.; Evans, D.T.; Poignard, P.; Hessell, A.J.; Burton, D.R. A panel of IgG 1 B12 variants with selectively diminished or enhanced affinity for fcgamma receptors to define the role of effector functions in protection against HIV. J. Virol. 2011, 85, 10572–10581. [CrossRef][PubMed]
107. Moldt, B.; Shibata-Koyama, M.; Rakasz, E.G.; Schultz, N.; Kanda, Y.; Dunlop, D.C.; Finstad, S.L.; Jin, C.; Landucci, G.; Alpert, M.D., et al. A nonfucosylated variant of the anti-HIV-1 monoclonal antibody B12 has enhanced fcgammariiia-mediated antiviral activity in vitro but does not improve protection against mucosal shiv challenge in macaques. J. Virol. 2012, 86, 6189–6196. [CrossRef][PubMed]
108. Ray, K.; Mengistu, M.; Yu, L.; Lewis, G.K.; Lakowicz, J.R.; DeVico, A.L. Antigenic properties of the HIV envelope on virions in solution. J. Virol. 2014, 88, 1795–1808. [CrossRef][PubMed]
109. Helseth, E.; Olshevsky, U.; Furman, C.; Sodroski, J. Human immunodeficiency virus type 1 gp120 envelope glycoprotein regions important for association with the gp41 transmembrane glycoprotein. J. Virol. 1991, 65, 2119–2123. [PubMed]
110. Thali, M.; Furman, C.; Helseth, E.; Repke, H.; Sodroski, J. Lack of correlation between soluble CD4-induced shedding of the human immunodeficiency virus type 1 exterior envelope glycoprotein and subsequent membrane fusion events. J. Virol. 1992, 66, 5516–5524. [PubMed]
111. Yang, X.; Mahony, E.; Holm, G.H.; Kassa, A.; Sodroski, J. Role of the gp120 inner domain beta-sandwich in the interaction between the human immunodeficiency virus envelope glycoprotein subunits. Virology 2003, 313, 117–125. [CrossRef]
112. Leavitt, M.; Park, E.J.; Sidorov, I.A.; Dimitrov, D.S.; Quinnan, G.V., Jr. Concordant modulation of neutralization resistance and high infectivity of the primary human immunodeficiency virus type 1 mn strain and definition of a potential gp41 binding site in gp120. J. Virol. 2003, 77, 560–570. [CrossRef][PubMed]
113. Sen, J.; Jacobs, A.; Caffrey, M. Role of the HIV gp120 conserved domain 5 in processing and viral entry. Biochemistry 2008, 47, 7788–7795. [CrossRef][PubMed]
114. Wang, J.; Sen, J.; Rong, L.; Caffrey, M. Role of the HIV gp120 conserved domain 1 in processing and viral entry. J. Biol. Chem. 2008, 283, 32644–32649. [CrossRef][PubMed]
115. Merk, A.; Subramaniam, S. HIV-1 envelope glycoprotein structure. Curr. Opin. Struct. Biol. 2013, 23, 268–276. [CrossRef][PubMed]
116. Alsahafi, N.; Debbeche, O.; Sodroski, J.; Finzi, A. Effects of the i559p gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. PLoS ONE 2015, 10, e0122111. [CrossRef][PubMed]
117. Nishimura, Y.; Igarashi, T.; Haigwood, N.L.; Sadjadpour, R.; Donau, O.K.; Buckler, C.; Plishka, R.J.; Buckler-White, A.; Martin, M.A. Transfer of neutralizing IgG to macaques 6 h but not 24 h after shiv infection confers sterilizing protection: Implications for HIV-1 vaccine development. Proc. Natl. Acad. Sci. USA 2003, 100, 15131–15136. [CrossRef][PubMed]
118. Girard, M.P.; Picot, V.; Longuet, C.; Nabel, G.J. Report of the cent gardes HIV vaccine conference: The b-cell response to HIV. Part 2: Non-neutralizing antibodies: Fondation merieux conference center, veyrier du lac, france 5–7 november 2012. Vaccine 2013, 31, 2984–2987. [CrossRef][PubMed]
119. Matthias, L.J.; Yam, P.T.; Jiang, X.M.; Vandegraaff, N.; Li, P.; Poumbourios, P.; Donoghue, N.; Hogg, P.J. Disulfide exchange in domain 2 of CD4 is required for entry of HIV-1. Nat. Immunol. 2002, 3, 727–732. [CrossRef][PubMed]
120. Matthias, L.J.; Yam, P.T.; Jiang, X.M.; Hogg, P.J. Disulfide exchange in CD4. BioFactors 2003, 17, 241–248. [CrossRef][PubMed]
121. Maekawa, A.; Schmidt, B.; Fazekas de St Groth, B.; Sanejouand, Y.H.; Hogg, P.J. Evidence for a domain-swapped CD4 dimer as the coreceptor for binding to class II mhc. J. Immunol. 2006, 176, 6873–6878. [CrossRef][PubMed]
122. Matthias, L.J.; Azimi, I.; Tabrett, C.A.; Hogg, P.J. Reduced monomeric CD4 is the preferred receptor for HIV. J. Biol. Chem. 2010, 285, 40793–40799. [CrossRef][PubMed]
123. Cerutti, N.; Killick, M.; Jugnarain, V.; Papathanasopoulos, M.; Capovilla, A. Disulfide reduction in CD4 domain 1 or 2 is essential for interaction with HIV glycoprotein 120 (gp120), which impairs thioredoxin-driven CD4 dimerization. J. Biol. Chem. 2014, 289, 10455–10465. [CrossRef][PubMed]
124. Schwartz, O.; Dautry-Varsat, A.; Goud, B.; Marechal, V.; Subtil, A.; Heard, J.M.; Danos, O. Human immunodeficiency virus type 1 nef induces accumulation of CD4 in early endosomes. J. Virol. 1995, 69, 528–533. [PubMed]
125. Willey, R.L.; Maldarelli, F.; Martin, M.A.; Strebel, K. Human immunodeficiency virus type 1 vpu protein induces rapid degradation of CD4. J. Virol. 1992, 66, 7193–7200. [PubMed]
126. Neil, S.J.; Zang, T.; Bieniasz, P.D. Tetherin inhibits retrovirus release and is antagonized by HIV-1 vpu. Nature 2008, 451, 425–430. [CrossRef][PubMed]
127. Van Damme, N.; Goff, D.; Katsura, C.; Jorgenson, R.L.; Mitchell, R.; Johnson, M.C.; Stephens, E.B.; Guatelli, J. The interferon-induced protein BST-2 restricts HIV-1 release and is downregulated from the cell surface by the viral vpu protein. Cell Host Microbe 2008, 3, 245–252. [CrossRef][PubMed]
128. Veillette, M.; Coutu, M.; Richard, J.; Batraville, L.A.; Dagher, O.; Bernard, N.; Tremblay, C.; Kaufmann, D.E.; Roger, M.; Finzi, A. The HIV-1 gp120 CD4-bound conformation is preferentially targeted by antibody-dependent cellular cytotoxicity-mediating antibodies in sera from HIV-1-infected individuals. J. Virol. 2015, 89, 545–551. [CrossRef][PubMed]
129. Alvarez, R.A.; Hamlin, R.E.; Monroe, A.; Moldt, B.; Hotta, M.T.; Rodriguez Caprio, G.; Fierer, D.S.; Simon, V.; Chen, B.K. HIV-1 vpu antagonism of tetherin inhibits antibody-dependent cellular cytotoxic responses by natural killer cells. J. Virol. 2014, 88, 6031–6046. [CrossRef][PubMed]
130. Arias, J.F.; Heyer, L.N.; von Bredow, B.; Weisgrau, K.L.; Moldt, B.; Burton, D.R.; Rakasz, E.G.; Evans, D.T. Tetherin antagonism by vpu protects HIV-infected cells from antibody-dependent cell-mediated cytotoxicity. Proc. Natl. Acad. Sci. USA 2014, 111, 6425–6430. [CrossRef][PubMed]
131. Batraville, L.A.; Richard, J.; Veillette, M.; Labbe, A.C.; Alary, M.; Guedou, F.; Kaufmann, D.E.; Poudrier, J.; Finzi, A.; Roger, M. Short communication: Anti-HIV-1 envelope immunoglobulin GS in blood and cervicovaginal samples of beninese commercial sex workers. AIDS Res. Hum. Retrovir. 2014, 30, 1145–1149. [CrossRef][PubMed]
132. Richard, J.; Veillette, M.; Batraville, L.A.; Coutu, M.; Chapleau, J.P.; Bonsignori, M.; Bernard, N.; Tremblay, C.; Roger, M.; Kaufmann, D.E., et al. Flow cytometry-based assay to study HIV-1 gp120 specific antibody-dependent cellular cytotoxicity responses. J. Virol. Methods 2014, 208, 107–114. [CrossRef][PubMed]
133. Veillette, M.; Coutu, M.; Richard, J.; Batraville, L.A.; Desormeaux, A.; Roger, M.; Finzi, A. Conformational evaluation of HIV-1 trimeric envelope glycoproteins using a cell-based elisa assay. J. Vis. Exp. 2014. [CrossRef][PubMed]
134. Zhao, Q.; Ma, L.; Jiang, S.; Lu, H.; Liu, S.; He, Y.; Strick, N.; Neamati, N.; Debnath, A.K. Identification of n-phenyl-n1-(2,2,6,6-tetramethyl-piperidin-4-yl)-oxalamides as a new class of HIV-1 entry inhibitors that prevent gp120 binding to CD4. Virology 2005, 339, 213–225. [CrossRef][PubMed]
135. LaLonde, J.M.; Kwon, Y.D.; Jones, D.M.; Sun, A.W.; Courter, J.R.; Soeta, T.; Kobayashi, T.; Princiotto, A.M.; Wu, X.; Schon, A., et al. Structure-based design, synthesis, and characterization of dual hotspot small-molecule HIV-1 entry inhibitors. J. Med. Chem. 2012, 55, 4382–4396. [CrossRef][PubMed]
136. Lalonde, J.M.; Le-Khac, M.; Jones, D.M.; Courter, J.R.; Park, J.; Schon, A.; Princiotto, A.M.; Wu, X.; Mascola, J.R.; Freire, E., et al. Structure-based design and synthesis of an HIV-1 entry inhibitor exploiting X-ray and thermodynamic characterization. ACS Med. Chem. Lett. 2013, 4, 338–343. [CrossRef][PubMed]
137. Madani, N.; Schon, A.; Princiotto, A.M.; Lalonde, J.M.; Courter, J.R.; Soeta, T.; Ng, D.; Wang, L.; Brower, E.T.; Xiang, S.H., et al. Small-molecule CD4 mimics interact with a highly conserved pocket on HIV-1 gp120. Structure 2008, 16, 1689–1701. [CrossRef][PubMed]
138. Kwong, P.D.; Wyatt, R.; Robinson, J.; Sweet, R.W.; Sodroski, J.; Hendrickson, W.A. Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody. Nature 1998, 393, 648–659. [PubMed]
139. Schon, A.; Madani, N.; Klein, J.C.; Hubicki, A.; Ng, D.; Yang, X.; Smith, A.B., III; Sodroski, J.; Freire, E. Thermodynamics of binding of a low-molecular-weight CD4 mimetic to HIV-1 gp120. Biochemistry 2006, 45, 10973–10980. [CrossRef][PubMed]
140. Madani, N.; Princiotto, A.M.; Schon, A.; LaLonde, J.; Feng, Y.; Freire, E.; Park, J.; Courter, J.R.; Jones, D.M.; Robinson, J., et al. CD4-mimetic small molecules sensitize human immunodeficiency virus to vaccine-elicited antibodies. J. Virol. 2014, 88, 6542–6555. [CrossRef][PubMed]
141. Decker, J.M.; Bibollet-Ruche, F.; Wei, X.; Wang, S.; Levy, D.N.; Wang, W.; Delaporte, E.; Peeters, M.; Derdeyn, C.A.; Allen, S., et al. Antigenic conservation and immunogenicity of the HIV coreceptor binding site. J. Exp. Med. 2005, 201, 1407–1419. [CrossRef][PubMed]
142. Martin, L.; Stricher, F.; Misse, D.; Sironi, F.; Pugniere, M.; Barthe, P.; Prado-Gotor, R.; Freulon, I.; Magne, X.; Roumestand, C., et al. Rational design of a CD4 mimic that inhibits HIV-1 entry and exposes cryptic neutralization epitopes. Nat. Biotechnol. 2003, 21, 71–76. [CrossRef][PubMed]
143. Van Herrewege, Y.; Morellato, L.; Descours, A.; Aerts, L.; Michiels, J.; Heyndrickx, L.; Martin, L.; Vanham, G. CD4 mimetic miniproteins: Potent anti-HIV compounds with promising activity as microbicides. J. Antimicrob. Chemother. 2008, 61, 818–826. [CrossRef][PubMed]
144. Acharya, P.; Luongo, T.S.; Louder, M.K.; McKee, K.; Yang, Y.; Kwon, Y.D.; Mascola, J.R.; Kessler, P.; Martin, L.; Kwong, P.D. Structural basis for highly effective HIV-1 neutralization by CD4-mimetic miniproteins revealed by 1.5 a cocrystal structure of gp120 and m48u1. Structure 2013, 21, 1018–1029. [CrossRef][PubMed]
145. Richard, J.; Veillette, M.; Brassard, N.; Iyer, S.S.; Roger, M.; Martin, L.; Pazgier, M.; Schon, A.; Freire, E.; Routy, J.P., et al. CD4 mimetics sensitize HIV-1-infected cells to adcc. Proc. Natl. Acad. Sci. USA 2015, 112, E2687–E2694. [CrossRef][PubMed]
146. Parren, P.W.; Mondor, I.; Naniche, D.; Ditzel, H.J.; Klasse, P.J.; Burton, D.R.; Sattentau, Q.J. Neutralization of human immunodeficiency virus type 1 by antibody to gp120 is determined primarily by occupancy of sites on the virion irrespective of epitope specificity. J. Virol. 1998, 72, 3512–3519. [PubMed]
147. Klasse, P.J.; Sattentau, Q.J. Occupancy and mechanism in antibody-mediated neutralization of animal viruses. J. Gen. Virol. 2002, 83, 2091–2108. [CrossRef][PubMed]
148. Munro, J.B.; Mothes, W. Structure and dynamics of the native HIV-1 Env trimer. J. Virol. 2015, 89, 5752–5755. [CrossRef][PubMed]