Human Non-neutralizing HIV-1 Envelope Monoclonal Antibodies Limit the Number of Founder Viruses during SHIV Mucosal Infection in Rhesus Macaques

PLoS Pathogens

Volumn 11, Issue 8, 2015, Pages

  Santra, Sampa ^a   Tomaras, Georgia D ^b   Warrier, Ranjit ^c   Nicely, Nathan I ^b   Liao, Hua Xin ^b   Pollara, Justin ^b   Liu, Pinghuang ^b   Alam, S Munir ^b   Zhang, Ruijun ^b   Cocklin, Sarah L ^a   Shen, Xiaoying ^b   Duffy, Ryan ^b   Xia, Shi Mao ^b   Schutte, Robert J ^b   Pemble IV, Charles W ^b   Dennison, S Moses ^b   Li, Hui ^c   Chao, Andrew ^c   Vidnovic, Kora ^c   Evans, Abbey ^d   Klein, Katja ^d   Kumar, Amit ^b   Robinson, James ^e   Landucci, Gary ^f   Forthal, Donald N ^f   Montefiori, David C ^b   Kaewkungwal, Jaranit ^g   Nitayaphan, Sorachai ^h   Pitisuttithum, Punnee ⁱ   Rerks Ngarm, Supachai ^j   Robb, Merlin L ^k   Michael, Nelson L ^k   Kim, Jerome H ^k,n   Soderberg, Kelly A ^b   Giorgi, Elena E ^l   Blair, Lily ^l   Korber, Bette T ^l   Moog, Christiane ^m   Shattock, Robin J ^d   Letvin, Norman L ^a   Schmitz, Joern E ^a   Moody, M A ^b   Gao, Feng ^b   Ferrari, Guido ^b   Shaw, George M ^c   Haynes, Barton F ^b   more..

^a HARVARD MEDICAL SCHOOL   (United States)

^b DUKE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c UNIVERSITY OF PENNSYLVANIA   (United States)

^d IMPERIAL COLLEGE LONDON   (United Kingdom)

^e TULANE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^f UNIVERSITY OF CALIFORNIA   (United States)

^g MAHIDOL UNIVERSITY   (Thailand)

^h ARMED FORCES RESEARCH INSTITUTE OF MEDICAL SCIENCES   (Thailand)

ⁱ MAHIDOL UNIVERSITY   (Thailand)

^j MINISTRY OF PUBLIC HEALTH   (Thailand)

^k WALTER REED ARMY INSTITUTE OF RESEARCH   (United States)

^l LOS ALAMOS NATIONAL LABORATORY   (United States)

^m UNIVERSITÉ DE STRASBOURG   (France)

ⁿ NONE   (South Korea)

more..

Author keywords

[No Author keywords available]

Indexed keywords

GLYCOPROTEIN GP 120; GLYCOPROTEIN GP 41; IMMUNOGLOBULIN FC FRAGMENT; MONOCLONAL ANTIBODY; VIRUS RNA; VIRUS ANTIBODY; VIRUS ENVELOPE PROTEIN;

ANIMAL EXPERIMENT; ANTIBODY DEPENDENT CELLULAR CYTOTOXICITY; ANTIGEN BINDING; ANTIGEN SPECIFICITY; ARTICLE; BINDING AFFINITY; CD4+ T LYMPHOCYTE; CONTROLLED STUDY; CRYSTALLOGRAPHY; DENDRITIC CELL; ENZYME LINKED IMMUNOSORBENT ASSAY; FLOW CYTOMETRY; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN TISSUE; IMMOBILIZED METAL AFFINITY CHROMATOGRAPHY; IMMUNOFLUORESCENCE TEST; LUCIFERASE ASSAY; NATURAL KILLER CELL; NONHUMAN; PERIPHERAL BLOOD MONONUCLEAR CELL; PERITONEUM MACROPHAGE; PHAGOCYTOSIS; PHYLOGENETIC TREE; REAL TIME POLYMERASE CHAIN REACTION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; RHESUS MONKEY; SEQUENCE ALIGNMENT; SEQUENCE ANALYSIS; SIMIAN ACQUIRED IMMUNODEFICIENCY SYNDROME; SURFACE PLASMON RESONANCE; VIRUS ENVELOPE; VIRUS GENOME; VIRUS LOAD; VIRUS NEUTRALIZATION; VIRUS TRANSMISSION; ANIMAL; CHEMISTRY; FLUORESCENT ANTIBODY TECHNIQUE; IMMUNOLOGY; INTESTINE MUCOSA; PROTEIN CONFORMATION; RECTUM; SIMIAN IMMUNODEFICIENCY VIRUS; VIROLOGY;

ANIMALS; ANTIBODIES, MONOCLONAL; ANTIBODIES, VIRAL; CD4-POSITIVE T-LYMPHOCYTES; FLUORESCENT ANTIBODY TECHNIQUE; HIV-1; HUMANS; INTESTINAL MUCOSA; MACACA MULATTA; PROTEIN CONFORMATION; RECTUM; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; SIMIAN ACQUIRED IMMUNODEFICIENCY SYNDROME; SIMIAN IMMUNODEFICIENCY VIRUS; SURFACE PLASMON RESONANCE; VIRAL ENVELOPE PROTEINS;

EID: 84940771125     PISSN: 15537366     EISSN: 15537374     Source Type: Journal    
DOI: 10.1371/journal.ppat.1005042     Document Type: Article

References (120)

1. Mascola JR, Haynes BF, (2013) HIV-1 neutralizing antibodies: understanding nature's pathways. Immunol Rev 254: 225–244. doi: 10.1111/imr.12075 23772623
2. Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, Kaewkungwal J, Chiu J, et al. (2009) Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N Engl J Med 361: 2209–2220. doi: 10.1056/NEJMoa0908492 19843557
3. Haynes BF, Gilbert PB, McElrath MJ, Zolla-Pazner S, Tomaras GD, et al. (2012) Immune-correlates analysis of an HIV-1 vaccine efficacy trial. N Engl J Med 366: 1275–1286. doi: 10.1056/NEJMoa1113425 22475592
4. Yates NL, Liao HX, Fong Y, deCamp A, Vandergrift NA, et al. (2014) Vaccine-induced Env V1-V2 IgG3 correlates with lower HIV-1 infection risk and declines soon after vaccination. Sci Transl Med 6: 228ra239.
5. Tomaras GD, Ferrari G, Shen X, Alam SM, Liao HX, et al. (2013) 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 U S A 110: 9019–9024. doi: 10.1073/pnas.1301456110 23661056
6. Tomaras GD, Haynes BF, (2014) Advancing Toward HIV-1 Vaccine Efficacy through the Intersections of Immune Correlates. Vaccines (Basel) 2: 15–35.
7. Tomaras GD, Haynes BF, (2010) Strategies for eliciting HIV-1 inhibitory antibodies. Curr Opin HIV AIDS 5: 421–427. doi: 10.1097/COH.0b013e32833d2d45 20978384
8. Haynes BF, Liao HX, Tomaras GD, (2010) Is developing an HIV-1 vaccine possible? Curr Opin HIV AIDS 5: 362–367. doi: 10.1097/COH.0b013e32833d2e90 20978375
9. Holl V, Peressin M, Decoville T, Schmidt S, Zolla-Pazner S, et al. (2006) Nonneutralizing antibodies are able to inhibit human immunodeficiency virus type 1 replication in macrophages and immature dendritic cells. J Virol 80: 6177–6181. 16731957
10. Nyambi PN, Mbah HA, Burda S, Williams C, Gorny MK, et al. (2000) Conserved and exposed epitopes on intact, native, primary human immunodeficiency virus type 1 virions of group M. J Virol 74: 7096–7107. 10888650
11. Liu P, Overman RG, Yates NL, Alam SM, Vandergrift N, et al. (2011) Dynamic antibody specificities and virion concentrations in circulating immune complexes in acute to chronic HIV-1 infection. J Virol 85: 11196–11207. doi: 10.1128/JVI.05601-11 21865397
12. Liu P, Williams LD, Shen X, Bonsignori M, Vandergrift NA, et al. (2014) Capacity for infectious HIV-1 virion capture differs by envelope antibody specificity. J Virol 88: 5165–5170. doi: 10.1128/JVI.03765-13 24554654
13. Moog C, Dereuddre-Bosquet N, Teillaud JL, Biedma ME, Holl V, et al. (2014) Protective effect of vaginal application of neutralizing and nonneutralizing inhibitory antibodies against vaginal SHIV challenge in macaques. Mucosal Immunol 7: 46–56. doi: 10.1038/mi.2013.23 23591718
14. Tyler DS, Stanley SD, Zolla-Pazner S, Gorny MK, Shadduck PP, et al. (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. 1700004
15. Pancera M, Zhou T, Druz A, Georgiev IS, Soto C, et al. (2014) Structure and immune recognition of trimeric pre-fusion HIV-1 Env. Nature 514: 455–461. doi: 10.1038/nature13808 25296255
16. He XM, Ruker F, Casale E, Carter DC, (1992) Structure of a human monoclonal antibody Fab fragment against gp41 of human immunodeficiency virus type 1. Proc Natl Acad Sci U S A 89: 7154–7158. 1496010
17. Stigler RD, Ruker F, Katinger D, Elliott G, Hohne W, et al. (1995) Interaction between a Fab fragment against gp41 of human immunodeficiency virus 1 and its peptide epitope: characterization using a peptide epitope library and molecular modeling. Protein Eng 8: 471–479. 8532669
18. Ferrari G, Pollara J, Kozink D, Harms T, Drinker M, et al. (2011) 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 85: 7029–7036. doi: 10.1128/JVI.00171-11 21543485
19. Guan Y, Pazgier M, Sajadi MM, Kamin-Lewis R, Al-Darmarki S, et al. (2013) Diverse specificity and effector function among human antibodies to HIV-1 envelope glycoprotein epitopes exposed by CD4 binding. Proc Natl Acad Sci U S A 110: E69–78. doi: 10.1073/pnas.1217609110 23237851
20. Bonsignori M, Pollara J, Moody MA, Alpert MD, Chen X, et al. (2012) 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 86: 11521–11532. doi: 10.1128/JVI.01023-12 22896626
21. Veillette M, Coutu M, Richard J, Batraville LA, Dagher O, et al. (2015) 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 89: 545–551. doi: 10.1128/JVI.02868-14 25339767
22. Veillette M, Desormeaux A, Medjahed H, Gharsallah NE, Coutu M, et al. (2014) Interaction with cellular CD4 exposes HIV-1 envelope epitopes targeted by antibody-dependent cell-mediated cytotoxicity. J Virol 88: 2633–2644. doi: 10.1128/JVI.03230-13 24352444
23. Acharya P, Tolbert WD, Gohain N, Wu X, Yu L, et al. (2014) Structural definition of an antibody-dependent cellular cytotoxicity response implicated in reduced risk for HIV-1 infection. J Virol 88: 12895–12906. doi: 10.1128/JVI.02194-14 25165110
24. McElrath MJ, Haynes BF, (2010) Induction of immunity to human immunodeficiency virus type-1 by vaccination. Immunity 33: 542–554. doi: 10.1016/j.immuni.2010.09.011 21029964
25. Shattock RJ, Haynes BF, Pulendran B, Flores J, Esparza J, et al. (2008) Improving defences at the portal of HIV entry: mucosal and innate immunity. PLoS Med 5: e81. doi: 10.1371/journal.pmed.0050081 18384232
26. Tomaras GD, Yates NL, Liu P, Qin L, Fouda GG, et al. (2008) Initial B-cell responses to transmitted human immunodeficiency virus type 1: virion-binding immunoglobulin M (IgM) and IgG antibodies followed by plasma anti-gp41 antibodies with ineffective control of initial viremia. J Virol 82: 12449–12463. doi: 10.1128/JVI.01708-08 18842730
27. Montefiori DC, (1997) Role of complement and Fc receptors in the pathogenesis of HIV-1 infection. Springer Semin Immunopathol 18: 371–390. 9089955
28. Willey S, Aasa-Chapman MM, O'Farrell S, Pellegrino P, Williams I, et al. (2011) Extensive complement-dependent enhancement of HIV-1 by autologous non-neutralising antibodies at early stages of infection. Retrovirology 8: 16. doi: 10.1186/1742-4690-8-16 21401915
29. Gupta S, Pegu P, Venzon DJ, Gach JS, Ma ZM, et al. (2014) Enhanced In Vitro Transcytosis of Simian Immunodeficiency Virus Mediated by Vaccine-Induced Antibody Predicts Transmitted/Founder Strain Number After Rectal Challenge. J Infect Dis.
30. Burton DR, Hessell AJ, Keele BF, Klasse PJ, Ketas TA, et al. (2011) 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 U S A 108: 11181–11186. doi: 10.1073/pnas.1103012108 21690411
31. Hessell AJ, Haigwood NL, (2012) Neutralizing antibodies and control of HIV: moves and countermoves. Curr HIV/AIDS Rep 9: 64–72. doi: 10.1007/s11904-011-0105-5 22203469
32. Hessell AJ, Hangartner L, Hunter M, Havenith CE, Beurskens FJ, et al. (2007) Fc receptor but not complement binding is important in antibody protection against HIV. Nature 449: 101–104. 17805298
33. Keele BF, Giorgi EE, Salazar-Gonzalez JF, Decker JM, Pham KT, et al. (2008) Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection. Proc Natl Acad Sci U S A 105: 7552–7557. doi: 10.1073/pnas.0802203105 18490657
34. Li H, Bar KJ, Wang S, Decker JM, Chen Y, et al. (2010) High Multiplicity Infection by HIV-1 in Men Who Have Sex with Men. PLoS Pathog 6: e1000890. doi: 10.1371/journal.ppat.1000890 20485520
35. Pincus SH, Fang H, Wilkinson RA, Marcotte TK, Robinson JE, et al. (2003) In vivo efficacy of anti-glycoprotein 41, but not anti-glycoprotein 120, immunotoxins in a mouse model of HIV infection. J Immunol 170: 2236–2241. 12574398
36. Montefiori DC, Karnasuta C, Huang Y, Ahmed H, Gilbert P, et al. (2012) Magnitude and breadth of the neutralizing antibody response in the RV144 and Vax003 HIV-1 vaccine efficacy trials. J Infect Dis 206: 431–441. doi: 10.1093/infdis/jis367 22634875
37. Tomaras GD, Binley JM, Gray ES, Crooks ET, Osawa K, et al. (2011) Polyclonal B cell responses to conserved neutralization epitopes in a subset of HIV-1-infected individuals. J Virol 85: 11502–11519. doi: 10.1128/JVI.05363-11 21849452
38. Du AP, Limal D, Semetey V, Dali H, Jolivet M, et al. (2002) Structural and immunological characterisation of heteroclitic peptide analogues corresponding to the 600–612 region of the HIV envelope gp41 glycoprotein. J Mol Biol 323: 503–521. 12381305
39. Oldstone MB, Tishon A, Lewicki H, Dyson HJ, Feher VA, et al. (1991) Mapping the anatomy of the immunodominant domain of the human immunodeficiency virus gp41 transmembrane protein: peptide conformation analysis using monoclonal antibodies and proton nuclear magnetic resonance spectroscopy. J Virol 65: 1727–1734. 2002540
40. Aydin H, Smrke BM, Lee JE, (2013) Structural characterization of a fusion glycoprotein from a retrovirus that undergoes a hybrid 2-step entry mechanism. FASEB J 27: 5059–5071. doi: 10.1096/fj.13-232371 24036886
41. Fass D, Harrison SC, Kim PS, (1996) Retrovirus envelope domain at 1.7 angstrom resolution. Nat Struct Biol 3: 465–469. 8612078
42. Maerz AL, Center RJ, Kemp BE, Kobe B, Poumbourios P, (2000) Functional implications of the human T-lymphotropic virus type 1 transmembrane glycoprotein helical hairpin structure. J Virol 74: 6614–6621. 10864675
43. Maerz AL, Drummer HE, Wilson KA, Poumbourios P, (2001) Functional analysis of the disulfide-bonded loop/chain reversal region of human immunodeficiency virus type 1 gp41 reveals a critical role in gp120-gp41 association. J Virol 75: 6635–6644. 11413331
44. Weissenhorn W, Carfi A, Lee KH, Skehel JJ, Wiley DC, (1998) Crystal structure of the Ebola virus membrane fusion subunit, GP2, from the envelope glycoprotein ectodomain. Mol Cell 2: 605–616. 9844633
45. Kobe B, Center RJ, Kemp BE, Poumbourios P, (1999) Crystal structure of human T cell leukemia virus type 1 gp21 ectodomain crystallized as a maltose-binding protein chimera reveals structural evolution of retroviral transmembrane proteins. Proc Natl Acad Sci U S A 96: 4319–4324. 10200260
46. Delos SE, La B, Gilmartin A, White JM, (2010) Studies of the "chain reversal regions" of the avian sarcoma/leukosis virus (ASLV) and ebolavirus fusion proteins: analogous residues are important, and a His residue unique to EnvA affects the pH dependence of ASLV entry. J Virol 84: 5687–5694. doi: 10.1128/JVI.02583-09 20335266
47. Caffrey M, Cai M, Kaufman J, Stahl SJ, Wingfield PT, et al. (1998) Three-dimensional solution structure of the 44 kDa ectodomain of SIV gp41. EMBO J 17: 4572–4584. 9707417
48. Caffrey M, (2001) Model for the structure of the HIV gp41 ectodomain: insight into the intermolecular interactions of the gp41 loop. Biochim Biophys Acta 1536: 116–122. 11406346
49. Colman PM, Laver WG, Varghese JN, Baker AT, Tulloch PA, et al. (1987) Three-dimensional structure of a complex of antibody with influenza virus neuraminidase. Nature 326: 358–363. 2436051
50. Rini JM, Schulze-Gahmen U, Wilson IA, (1992) Structural evidence for induced fit as a mechanism for antibody-antigen recognition. Science 255: 959–965. 1546293
51. Stanfield RL, Wilson IA, (1995) Protein-peptide interactions. Curr Opin Struct Biol 5: 103–113. 7773739
52. Jimenez R, Salazar G, Baldridge KK, Romesberg FE, (2003) Flexibility and molecular recognition in the immune system. Proc Natl Acad Sci U S A 100: 92–97. 12518056
53. Boehr DD, Nussinov R, Wright PE, (2009) The role of dynamic conformational ensembles in biomolecular recognition. Nat Chem Biol 5: 789–796. doi: 10.1038/nchembio.232 19841628
54. Moore PL, Crooks ET, Porter L, Zhu P, Cayanan CS, et al. (2006) Nature of nonfunctional envelope proteins on the surface of human immunodeficiency virus type 1. J Virol 80: 2515–2528. 16474158
55. Poignard P, Moulard M, Golez E, Vivona V, Franti M, et al. (2003) Heterogeneity of envelope molecules expressed on primary human immunodeficiency virus type 1 particles as probed by the binding of neutralizing and nonneutralizing antibodies. J Virol 77: 353–365. 12477840
56. Pancera M, Wyatt R, (2005) Selective recognition of oligomeric HIV-1 primary isolate envelope glycoproteins by potently neutralizing ligands requires efficient precursor cleavage. Virology 332: 145–156. 15661147
57. Dey AK, David KB, Ray N, Ketas TJ, Klasse PJ, et al. (2008) N-terminal substitutions in HIV-1 gp41 reduce the expression of non-trimeric envelope glycoproteins on the virus. Virology 372: 187–200. 18031785
58. Herrera C, Spenlehauer C, Fung MS, Burton DR, Beddows S, et al. (2003) Nonneutralizing antibodies to the CD4-binding site on the gp120 subunit of human immunodeficiency virus type 1 do not interfere with the activity of a neutralizing antibody against the same site. J Virol 77: 1084–1091. 12502824
59. Burrer R, Haessig-Einius S, Aubertin AM, Moog C, (2005) Neutralizing as well as non-neutralizing polyclonal immunoglobulin (Ig)G from infected patients capture HIV-1 via antibodies directed against the principal immunodominant domain of gp41. Virology 333: 102–113. 15708596
60. Shields RL, Namenuk AK, Hong K, Meng YG, Rae J, et al. (2001) High resolution mapping of the binding site on human IgG1 for Fc gamma RI, Fc gamma RII, Fc gamma RIII, and FcRn and design of IgG1 variants with improved binding to the Fc gamma R. J Biol Chem 276: 6591–6604. 11096108
61. Richards JO, Karki S, Lazar GA, Chen H, Dang W, et al. (2008) Optimization of antibody binding to FcgammaRIIa enhances macrophage phagocytosis of tumor cells. Mol Cancer Ther 7: 2517–2527. doi: 10.1158/1535-7163.MCT-08-0201 18723496
62. Maenaka K, van der Merwe PA, Stuart DI, Jones EY, Sondermann P, (2001) The human low affinity Fcgamma receptors IIa, IIb, and III bind IgG with fast kinetics and distinct thermodynamic properties. J Biol Chem 276: 44898–44904. 11544262
63. Paetz A, Sack M, Thepen T, Tur MK, Bruell D, et al. (2005) Recombinant soluble human Fcgamma receptor I with picomolar affinity for immunoglobulin G. Biochem Biophys Res Commun 338: 1811–1817. 16289041
64. Liu P, Yates NL, Shen X, Bonsignori M, Moody MA, et al. (2013) Infectious virion capture by HIV-1 gp120-specific IgG from RV144 vaccinees. J Virol 87: 7828–7836. doi: 10.1128/JVI.02737-12 23658446
65. Liao HX, Bonsignori M, Alam SM, McLellan JS, Tomaras GD, et al. (2013) Vaccine induction of antibodies against a structurally heterogeneous site of immune pressure within HIV-1 envelope protein variable regions 1 and 2. Immunity 38: 176–186. doi: 10.1016/j.immuni.2012.11.011 23313589
66. Fletcher PS, Elliott J, Grivel JC, Margolis L, Anton P, et al. (2006) Ex vivo culture of human colorectal tissue for the evaluation of candidate microbicides. AIDS 20: 1237–1245. 16816551
67. Hessell AJ, Rakasz EG, Tehrani DM, Huber M, Weisgrau KL, et al. (2010) 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 84: 1302–1313. doi: 10.1128/JVI.01272-09 19906907
68. Whittle JR, Zhang R, Khurana S, King LR, Manischewitz J, et al. (2011) Broadly neutralizing human antibody that recognizes the receptor-binding pocket of influenza virus hemagglutinin. Proc Natl Acad Sci U S A 108: 14216–14221. doi: 10.1073/pnas.1111497108 21825125
69. Abrahams MR, Anderson JA, Giorgi EE, Seoighe C, Mlisana K, et al. (2009) Quantitating the multiplicity of infection with human immunodeficiency virus type 1 subtype C reveals a non-poisson distribution of transmitted variants. J Virol 83: 3556–3567. doi: 10.1128/JVI.02132-08 19193811
70. Haaland RE, Hawkins PA, Salazar-Gonzalez J, Johnson A, Tichacek A, et al. (2009) Inflammatory genital infections mitigate a severe genetic bottleneck in heterosexual transmission of subtype A and C HIV-1. PLoS Pathog 5: e1000274. doi: 10.1371/journal.ppat.1000274 19165325
71. Bar KJ, Li H, Chamberland A, Tremblay C, Routy JP, et al. (2010) Wide variation in the multiplicity of HIV-1 infection among injection drug users. J Virol 84: 6241–6247. doi: 10.1128/JVI.00077-10 20375173
72. Masharsky AE, Dukhovlinova EN, Verevochkin SV, Toussova OV, Skochilov RV, et al. (2010) A substantial transmission bottleneck among newly and recently HIV-1-infected injection drug users in St Petersburg, Russia. J Infect Dis 201: 1697–1702. doi: 10.1086/652702 20423223
73. Keele BF, Li H, Learn GH, Hraber P, Giorgi EE, et al. (2009) Low-dose rectal inoculation of rhesus macaques by SIVsmE660 or SIVmac251 recapitulates human mucosal infection by HIV-1. J Exp Med 206: 1117–1134. doi: 10.1084/jem.20082831 19414559
74. Finzi A, Xiang SH, Pacheco B, Wang L, Haight J, et al. (2010) Topological layers in the HIV-1 gp120 inner domain regulate gp41 interaction and CD4-triggered conformational transitions. Mol Cell 37: 656–667. doi: 10.1016/j.molcel.2010.02.012 20227370
75. Giorgi EE, Funkhouser B, Athreya G, Perelson AS, Korber BT, et al. (2010) Estimating time since infection in early homogeneous HIV-1 samples using a poisson model. BMC Bioinformatics 11: 532. doi: 10.1186/1471-2105-11-532 20973976
76. Butler DM, Smith DM, Cachay ER, Hightower GK, Nugent CT, et al. (2008) Herpes simplex virus 2 serostatus and viral loads of HIV-1 in blood and semen as risk factors for HIV transmission among men who have sex with men. AIDS 22: 1667–1671. doi: 10.1097/QAD.0b013e32830bfed8 18670228
77. Moldt B, Shibata-Koyama M, Rakasz EG, Schultz N, Kanda Y, et al. (2012) 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 86: 6189–6196. doi: 10.1128/JVI.00491-12 22457527
78. Ko SY, Pegu A, Rudicell RS, Yang ZY, Joyce MG, et al. (2014) Enhanced neonatal Fc receptor function improves protection against primate SHIV infection. Nature 514: 642–645. doi: 10.1038/nature13612 25119033
79. Li Q, Zeng M, Duan L, Voss JE, Smith AJ, et al. (2014) Live simian immunodeficiency virus vaccine correlate of protection: local antibody production and concentration on the path of virus entry. J Immunol 193: 3113–3125. doi: 10.4049/jimmunol.1400820 25135832
80. Bomsel M, Tudor D, Drillet AS, Alfsen A, Ganor Y, et al. (2011) Immunization with HIV-1 gp41 subunit virosomes induces mucosal antibodies protecting nonhuman primates against vaginal SHIV challenges. Immunity 34: 269–280. doi: 10.1016/j.immuni.2011.01.015 21315623
81. Shen R, Drelichman ER, Bimczok D, Ochsenbauer C, Kappes JC, et al. (2010) GP41-specific antibody blocks cell-free HIV type 1 transcytosis through human rectal mucosa and model colonic epithelium. J Immunol 184: 3648–3655. doi: 10.4049/jimmunol.0903346 20208001
82. Gottardo R, Bailer RT, Korber BT, Gnanakaran S, Phillips J, et al. (2013) Plasma IgG to linear epitopes in the V2 and V3 regions of HIV-1 gp120 correlate with a reduced risk of infection in the RV144 vaccine efficacy trial. PLoS One 8: e75665. doi: 10.1371/journal.pone.0075665 24086607
83. Moldt B, Rakasz EG, Schultz N, Chan-Hui PY, Swiderek K, et al. (2012) Highly potent HIV-specific antibody neutralization in vitro translates into effective protection against mucosal SHIV challenge in vivo. Proc Natl Acad Sci U S A 109: 18921–18925. doi: 10.1073/pnas.1214785109 23100539
84. Cao J, Bergeron L, Helseth E, Thali M, Repke H, et al. (1993) Effects of amino acid changes in the extracellular domain of the human immunodeficiency virus type 1 gp41 envelope glycoprotein. J Virol 67: 2747–2755. 8474172
85. Sattentau QJ, Moore JP, Vignaux F, Traincard F, Poignard P, (1993) Conformational changes induced in the envelope glycoproteins of the human and simian immunodeficiency viruses by soluble receptor binding. J Virol 67: 7383–7393. 7693970
86. Binley JM, Sanders RW, Clas B, Schuelke N, Master A, et al. (2000) A recombinant human immunodeficiency virus type 1 envelope glycoprotein complex stabilized by an intermolecular disulfide bond between the gp120 and gp41 subunits is an antigenic mimic of the trimeric virion-associated structure. J Virol 74: 627–643. 10623724
87. Kwong PD, Mascola JR, (2012) Human antibodies that neutralize HIV-1: identification, structures, and B cell ontogenies. Immunity 37: 412–425. doi: 10.1016/j.immuni.2012.08.012 22999947
88. Alam SM, McAdams M, Boren D, Rak M, Scearce RM, et al. (2007) The role of antibody polyspecificity and lipid reactivity in binding of broadly neutralizing anti-HIV-1 envelope human monoclonal antibodies 2F5 and 4E10 to glycoprotein 41 membrane proximal envelope epitopes. J Immunol 178: 4424–4435. 17372000
89. Haynes BF, Fleming J, St Clair EW, Katinger H, Stiegler G, et al. (2005) Cardiolipin polyspecific autoreactivity in two broadly neutralizing HIV-1 antibodies. Science 308: 1906–1908. 15860590
90. North B, Lehmann A, Dunbrack RL, Jr. (2011) A new clustering of antibody CDR loop conformations. J Mol Biol 406: 228–256. doi: 10.1016/j.jmb.2010.10.030 21035459
91. Goepfert PA, Elizaga ML, Seaton K, Tomaras GD, Montefiori DC, et al. (2014) Specificity and 6-month durability of immune responses induced by DNA and recombinant modified vaccinia Ankara vaccines expressing HIV-1 virus-like particles. J Infect Dis 210: 99–110. doi: 10.1093/infdis/jiu003 24403557
92. Hammer SM, Sobieszczyk ME, Janes H, Karuna ST, Mulligan MJ, et al. (2013) Efficacy trial of a DNA/rAd5 HIV-1 preventive vaccine. N Engl J Med 369: 2083–2092. doi: 10.1056/NEJMoa1310566 24099601
93. Liao HX, Levesque MC, Nagel A, Dixon A, Zhang R, et al. (2009) High-throughput isolation of immunoglobulin genes from single human B cells and expression as monoclonal antibodies. J Virol Methods 158: 171–179. doi: 10.1016/j.jviromet.2009.02.014 19428587
94. Wyatt R, Moore J, Accola M, Desjardin E, Robinson J, et al. (1995) Involvement of the V1/V2 variable loop structure in the exposure of human immunodeficiency virus type 1 gp120 epitopes induced by receptor binding. J Virol 69: 5723–5733. 7543586
95. Yates NL, Stacey AR, Nolen TL, Vandergrift NA, Moody MA, et al. (2013) HIV-1 gp41 envelope IgA is frequently elicited after transmission but has an initial short response half-life. Mucosal Immunol 6: 692–703. doi: 10.1038/mi.2012.107 23299618
96. Alam SM, Scearce RM, Parks RJ, Plonk K, Plonk SG, et al. (2008) Human immunodeficiency virus type 1 gp41 antibodies that mask membrane proximal region epitopes: antibody binding kinetics, induction, and potential for regulation in acute infection. J Virol 82: 115–125. 17942537
97. Liao HX, Chen X, Munshaw S, Zhang R, Marshall DJ, et al. (2011) Initial antibodies binding to HIV-1 gp41 in acutely infected subjects are polyreactive and highly mutated. J Exp Med 208: 2237–2249. doi: 10.1084/jem.20110363 21987658
98. Shen X, Duffy R, Howington R, Cope A, Sadagopal S, et al. (2015) Vaccine Induced Epitope Specific Antibodies to SIVmac239 Envelope Are Distinct from Those Induced to the HIV-1 Envelope in Non-Human Primates. J Virol.
99. Otwinowski A, Minor W, (1997) Processing of X-ray Diffraction Data Collected in Oscillation Mode. Methods in Enzymology 276: Macromolecular Crystallography, part A: 307–326.
100. Matthews BW, (1968) Solvent content of protein crystals. J Mol Biol 33: 491–497. 5700707
101. Terwilliger TC, Grosse-Kunstleve RW, Afonine PV, Moriarty NW, Zwart PH, et al. (2008) Iterative model building, structure refinement and density modification with the PHENIX AutoBuild wizard. Acta Crystallogr D Biol Crystallogr 64: 61–69. 18094468
102. Larson SB, Day JS, Glaser S, Braslawsky G, McPherson A, (2005) The structure of an antitumor C(H)2-domain-deleted humanized antibody. J Mol Biol 348: 1177–1190. 15854653
103. Appleton BA, Wu P, Maloney J, Yin J, Liang WC, et al. (2007) Structural studies of neuropilin/antibody complexes provide insights into semaphorin and VEGF binding. EMBO J 26: 4902–4912. 17989695
104. Emsley P, Lohkamp B, Scott WG, Cowtan K, (2010) Features and development of Coot. Acta Crystallogr D Biol Crystallogr 66: 486–501. doi: 10.1107/S0907444910007493 20383002
105. Adams PD, Afonine PV, Bunkoczi G, Chen VB, Davis IW, et al. (2010) PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr D Biol Crystallogr 66: 213–221. doi: 10.1107/S0907444909052925 20124702
106. Lovell SC, Davis IW, Arendall WB, 3rdde Bakker PI, Word JM, et al. (2003) Structure validation by Calpha geometry: phi,psi and Cbeta deviation. Proteins 50: 437–450. 12557186
107. Verkoczy L, Moody MA, Holl TM, Bouton-Verville H, Scearce RM, et al. (2009) Functional, non-clonal IgMa-restricted B cell receptor interactions with the HIV-1 envelope gp41 membrane proximal external region. PLoS One 4: e7215. doi: 10.1371/journal.pone.0007215 19806186
108. Webster RL, Johnson RP, (2005) Delineation of multiple subpopulations of natural killer cells in rhesus macaques. Immunology 115: 206–214. 15885126
109. Moody MA, Liao HX, Alam SM, Scearce RM, Plonk MK, et al. (2010) Anti-phospholipid human monoclonal antibodies inhibit CCR5-tropic HIV-1 and induce beta-chemokines. J Exp Med 207: 763–776. doi: 10.1084/jem.20091281 20368576
110. Li M, Gao F, Mascola JR, Stamatatos L, Polonis VR, et al. (2005) Human immunodeficiency virus type 1 env clones from acute and early subtype B infections for standardized assessments of vaccine-elicited neutralizing antibodies. J Virol 79: 10108–10125. 16051804
111. Adachi A, Gendelman HE, Koenig S, Folks T, Willey R, et al. (1986) Production of acquired immunodeficiency syndrome-associated retrovirus in human and nonhuman cells transfected with an infectious molecular clone. J Virol 59: 284–291. 3016298
112. Edmonds TG, Ding H, Yuan X, Wei Q, Smith KS, et al. (2010) Replication competent molecular clones of HIV-1 expressing Renilla luciferase facilitate the analysis of antibody inhibition in PBMC. Virology 408: 1–13. doi: 10.1016/j.virol.2010.08.028 20863545
113. O'Doherty U, Swiggard WJ, Malim MH, (2000) Human immunodeficiency virus type 1 spinoculation enhances infection through virus binding. J Virol 74: 10074–10080. 11024136
114. Pollara J, Bonsignori M, Moody MA, Liu P, Alam SM, et al. (2014) HIV-1 Vaccine-Induced C1 and V2 Env-Specific Antibodies Synergize for Increased Antiviral Activities. J Virol 88: 7715–7726. doi: 10.1128/JVI.00156-14 24807721
115. Shen X, Dennison SM, Liu P, Gao F, Jaeger F, et al. (2010) Prolonged exposure of the HIV-1 gp41 membrane proximal region with L669S substitution. Proc Natl Acad Sci U S A 107: 5972–5977. doi: 10.1073/pnas.0912381107 20231447
116. Leaman DP, Kinkead H, Zwick MB, (2010) In-solution virus capture assay helps deconstruct heterogeneous antibody recognition of human immunodeficiency virus type 1. J Virol 84: 3382–3395. doi: 10.1128/JVI.02363-09 20089658
117. Klein K, Veazey RS, Warrier R, Hraber P, Doyle-Meyers LA, et al. (2013) Neutralizing IgG at the portal of infection mediates protection against vaginal simian/human immunodeficiency virus challenge. J Virol 87: 11604–11616. doi: 10.1128/JVI.01361-13 23966410
118. Lee HY, Giorgi EE, Keele BF, Gaschen B, Athreya GS, et al. (2009) Modeling sequence evolution in acute HIV-1 infection. J Theor Biol 261: 341–360. doi: 10.1016/j.jtbi.2009.07.038 19660475
119. Rose PP, Korber BT, (2000) Detecting hypermutations in viral sequences with an emphasis on G—> A hypermutation. Bioinformatics 16: 400–401. 10869039
120. Pal R, Taylor B, Foulke JS, Woodward R, Merges M, et al. (2003) Characterization of a simian human immunodeficiency virus encoding the envelope gene from the CCR5-tropic HIV-1 Ba-L. J Acquir Immune Defic Syndr 33: 300–307. 12843740