Somatic mutations of the immunoglobulin framework are generally required for broad and potent HIV-1 neutralization

Cell

Volumn 153, Issue 1, 2013, Pages 126-138

  Klein, Florian ^a   Diskin, Ron ^b,c   Scheid, Johannes F ^a,d   Gaebler, Christian ^a,e   Mouquet, Hugo ^a   Georgiev, Ivelin S ^f   Pancera, Marie ^f   Zhou, Tongqing ^f   Incesu, Reha Baris ^a,g   Fu, Brooks Zhongzheng ^b   Gnanapragasam, Priyanthi N P ^b   Oliveira, Thiago Y ^a,h   Seaman, Michael S ⁱ   Kwong, Peter D ^f   Bjorkman, Pamela J ^b   Nussenzweig, Michel C ^a  

^a ROCKEFELLER UNIVERSITY   (United States)

^b CALIFORNIA INSTITUTE OF TECHNOLOGY   (United States)

^c WEIZMANN INSTITUTE OF SCIENCE   (Israel)

^d CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^e DRESDEN UNIVERSITY OF TECHNOLOGY   (Germany)

^f NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES   (United States)

^g UNIVERSITY MEDICAL CENTER HAMBURG EPPENDORF   (Germany)

^h UNIVERSITY OF SÃO PAULO   (Brazil)

ⁱ BETH ISRAEL DEACONESS MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIGEN; IMMUNOGLOBULIN; NEUTRALIZING ANTIBODY;

ARTICLE; FRAMEWORK REGION; GENETIC PARAMETERS; HUMAN IMMUNODEFICIENCY VIRUS 1; NONHUMAN; PRIORITY JOURNAL; SOMATIC MUTATION; STRUCTURE ANALYSIS; VIRUS NEUTRALIZATION;

EID: 84875759341     PISSN: 00928674     EISSN: 10974172     Source Type: Journal    
DOI: 10.1016/j.cell.2013.03.018     Document Type: Article

References (78)

1. P.D. Adams, P.V. Afonine, G. Bunkóczi, V.B. Chen, I.W. Davis, N. Echols, J.J. Headd, L.W. Hung, G.J. Kapral, and R.W. Grosse-Kunstleve PHENIX: a comprehensive Python-based system for macromolecular structure solution Acta Crystallogr. D Biol. Crystallogr. 66 2010 213 221
2. A.G. Amit, R.A. Mariuzza, S.E. Phillips, and R.J. Poljak Three-dimensional structure of an antigen-antibody complex at 2.8 A resolution Science 233 1986 747 753 (Pubitemid 16016225)
3. L.M. Amzel, and R.J. Poljak Three-dimensional structure of immunoglobulins Annu. Rev. Biochem. 48 1979 961 997 (Pubitemid 10191101)
4. F.D. Batista, and M.S. Neuberger Affinity dependence of the B cell response to antigen: a threshold, a ceiling, and the importance of off-rate Immunity 8 1998 751 759 (Pubitemid 28294522)
5. A. Buchacher, R. Predl, K. Strutzenberger, W. Steinfellner, A. Trkola, M. Purtscher, G. Gruber, C. Tauer, F. Steindl, and A. Jungbauer Generation of human monoclonal antibodies against HIV-1 proteins; electrofusion and Epstein-Barr virus transformation for peripheral blood lymphocyte immortalization AIDS Res. Hum. Retroviruses 10 1994 359 369 (Pubitemid 24141210)
6. D.A. Calarese, C.N. Scanlan, M.B. Zwick, S. Deechongkit, Y. Mimura, R. Kunert, P. Zhu, M.R. Wormald, R.L. Stanfield, and K.H. Roux Antibody domain exchange is an immunological solution to carbohydrate cluster recognition Science 300 2003 2065 2071 (Pubitemid 36760127)
7. D. Corti, J.P. Langedijk, A. Hinz, M.S. Seaman, F. Vanzetta, B.M. Fernandez-Rodriguez, C. Silacci, D. Pinna, D. Jarrossay, and S. Balla-Jhagjhoorsingh Analysis of memory B cell responses and isolation of novel monoclonal antibodies with neutralizing breadth from HIV-1-infected individuals PLoS ONE 5 2010 e8805
8. R. Diskin, J.F. Scheid, P.M. Marcovecchio, A.P. West Jr., F. Klein, H. Gao, P.N. Gnanapragasam, A. Abadir, M.S. Seaman, M.C. Nussenzweig, and P.J. Bjorkman Increasing the potency and breadth of an HIV antibody by using structure-based rational design Science 334 2011 1289 1293
9. N.A. Doria-Rose, R.M. Klein, M.G. Daniels, S. O'Dell, M. Nason, A. Lapedes, T. Bhattacharya, S.A. Migueles, R.T. Wyatt, and B.T. Korber Breadth of human immunodeficiency virus-specific neutralizing activity in sera: clustering analysis and association with clinical variables J. Virol. 84 2010 1631 1636
10. P. Emsley, B. Lohkamp, W.G. Scott, and K. Cowtan Features and development of Coot Acta Crystallogr. D Biol. Crystallogr. 66 2010 486 501
11. J. Foote, and C. Milstein Kinetic maturation of an immune response Nature 352 1991 530 532 (Pubitemid 21912377)
12. V. Giudicelli, P. Duroux, C. Ginestoux, G. Folch, J. Jabado-Michaloud, D. Chaume, and M.P. Lefranc IMGT/LIGM-DB, the IMGT comprehensive database of immunoglobulin and T cell receptor nucleotide sequences Nucleic Acids Res. 34 Database issue 2006 D781 D784
13. M.K. Gorny, J.Y. Xu, S. Karwowska, A. Buchbinder, and S. Zolla-Pazner Repertoire of neutralizing human monoclonal antibodies specific for the V3 domain of HIV-1 gp120 J. Immunol. 150 1993 635 643 (Pubitemid 23133641)
14. J. Huang, G. Ofek, L. Laub, M.K. Louder, N.A. Doria-Rose, N.S. Longo, H. Imamichi, R.T. Bailer, B. Chakrabarti, and S.K. Sharma Broad and potent neutralization of HIV-1 by a gp41-specific human antibody Nature 491 2012 406 412
15. M. Huber, K.M. Le, K.J. Doores, Z. Fulton, R.L. Stanfield, I.A. Wilson, and D.R. Burton Very few substitutions in a germ line antibody are required to initiate significant domain exchange J. Virol. 84 2010 10700 10707
16. C.J. Jolly, S.D. Wagner, C. Rada, N. Klix, C. Milstein, and M.S. Neuberger The targeting of somatic hypermutation Semin. Immunol. 8 1996 159 168 (Pubitemid 26169618)
17. P.T. Jones, P.H. Dear, J. Foote, M.S. Neuberger, and G. Winter Replacing the complementarity-determining regions in a human antibody with those from a mouse Nature 321 1986 522 525 (Pubitemid 16052256)
18. E. Kabat, T.T. Wu, M. Reid-Miller, H.M. Perry, K.S. Gottesman, and C. Foeller Sequences of Proteins of Immunological Interest 1991 US Department of Health and Human Services, National Institutes of Health Bethesda, MD
19. W. Kabsch Integration, scaling, space-group assignment and post-refinement Acta Crystallogr. D Biol. Crystallogr. 66 2010 133 144
20. F. Klein, C. Gaebler, H. Mouquet, D.N. Sather, C. Lehmann, J.F. Scheid, Z. Kraft, Y. Liu, J. Pietzsch, and A. Hurley Broad neutralization by a combination of antibodies recognizing the CD4 binding site and a new conformational epitope on the HIV-1 envelope protein J. Exp. Med. 209 2012 1469 1479
21. F. Klein, A. Halper-Stromberg, J.A. Horwitz, H. Gruell, J.F. Scheid, S. Bournazos, H. Mouquet, L.A. Spatz, R. Diskin, and A. Abadir HIV therapy by a combination of broadly neutralizing antibodies in humanized mice Nature 492 2012 118 122
22. M.P. Lefranc, V. Giudicelli, C. Ginestoux, J. Bodmer, W. Müller, R. Bontrop, M. Lemaitre, A. Malik, V. Barbié, and D. Chaume IMGT, the international ImMunoGeneTics database Nucleic Acids Res. 27 1999 209 212 (Pubitemid 29209441)
23. M. Li, F. Gao, J.R. Mascola, L. Stamatatos, V.R. Polonis, M. Koutsoukos, G. Voss, P. Goepfert, P. Gilbert, and K.M. Greene 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 2005 10108 10125 (Pubitemid 41098552)
24. J.R. Mascola, G. Stiegler, T.C. VanCott, H. Katinger, C.B. Carpenter, C.E. Hanson, H. Beary, D. Hayes, S.S. Frankel, D.L. Birx, and M.G. Lewis Protection of macaques against vaginal transmission of a pathogenic HIV-1/SIV chimeric virus by passive infusion of neutralizing antibodies Nat. Med. 6 2000 207 210 (Pubitemid 30082367)
25. A.J. McCoy, R.W. Grosse-Kunstleve, P.D. Adams, M.D. Winn, L.C. Storoni, and R.J. Read Phaser crystallographic software J. Appl. Cryst. 40 2007 658 674 (Pubitemid 47080256)
26. I. Mikell, D.N. Sather, S.A. Kalams, M. Altfeld, G. Alter, and L. Stamatatos Characteristics of the earliest cross-neutralizing antibody response to HIV-1 PLoS Pathog. 7 2011 e1001251
27. B. Moldt, E.G. Rakasz, N. Schultz, P.Y. Chan-Hui, K. Swiderek, K.L. Weisgrau, S.M. Piaskowski, Z. Bergman, D.I. Watkins, P. Poignard, and D.R. Burton Highly potent HIV-specific antibody neutralization in vitro translates into effective protection against mucosal SHIV challenge in vivo Proc. Natl. Acad. Sci. USA 109 2012 18921 18925
28. D.C. Montefiori Evaluating neutralizing antibodies against HIV, SIV, and SHIV in luciferase reporter gene assays Curr. Protoc. Immunol. 2005 Chapter 12, Unit 12 11
29. L. Morris, X. Chen, M. Alam, G. Tomaras, R. Zhang, D.J. Marshall, B. Chen, R. Parks, A. Foulger, and F. Jaeger Isolation of a human anti-HIV gp41 membrane proximal region neutralizing antibody by antigen-specific single B cell sorting PLoS ONE 6 2011 e23532
30. H. Mouquet, J.F. Scheid, M.J. Zoller, M. Krogsgaard, R.G. Ott, S. Shukair, M.N. Artyomov, J. Pietzsch, M. Connors, and F. Pereyra Polyreactivity increases the apparent affinity of anti-HIV antibodies by heteroligation Nature 467 2010 591 595
31. H. Mouquet, F. Klein, J.F. Scheid, M. Warncke, J. Pietzsch, T.Y. Oliveira, K. Velinzon, M.S. Seaman, and M.C. Nussenzweig Memory B cell antibodies to HIV-1 gp140 cloned from individuals infected with clade A and B viruses PLoS ONE 6 2011 e24078
32. H. Mouquet, L. Scharf, Z. Euler, Y. Liu, C. Eden, J.F. Scheid, A. Halper-Stromberg, P.N. Gnanapragasam, D.I. Spencer, and M.S. Seaman Complex-type N-glycan recognition by potent broadly neutralizing HIV antibodies Proc. Natl. Acad. Sci. USA 109 2012 E3268 E3277
33. T. Muster, F. Steindl, M. Purtscher, A. Trkola, A. Klima, G. Himmler, F. Rüker, and H. Katinger A conserved neutralizing epitope on gp41 of human immunodeficiency virus type 1 J. Virol. 67 1993 6642 6647 (Pubitemid 23309131)
34. R. Pavri, and M.C. Nussenzweig AID targeting in antibody diversity Adv. Immunol. 110 2011 1 26
35. R. Pejchal, K.J. Doores, L.M. Walker, R. Khayat, P.S. Huang, S.K. Wang, R.L. Stanfield, J.P. Julien, A. Ramos, and M. Crispin A potent and broad neutralizing antibody recognizes and penetrates the HIV glycan shield Science 334 2011 1097 1103
36. J.U. Peled, F.L. Kuang, M.D. Iglesias-Ussel, S. Roa, S.L. Kalis, M.F. Goodman, and M.D. Scharff The biochemistry of somatic hypermutation Annu. Rev. Immunol. 26 2008 481 511 (Pubitemid 351600383)
37. J. Pietzsch, J.F. Scheid, H. Mouquet, F. Klein, M.S. Seaman, M. Jankovic, D. Corti, A. Lanzavecchia, and M.C. Nussenzweig Human anti-HIV-neutralizing antibodies frequently target a conserved epitope essential for viral fitness J. Exp. Med. 207 2010 1995 2002
38. K. Rajewsky Clonal selection and learning in the antibody system Nature 381 1996 751 758 (Pubitemid 26243107)
39. C.A. Reynaud, C. Garcia, W.R. Hein, and J.C. Weill Hypermutation generating the sheep immunoglobulin repertoire is an antigen-independent process Cell 80 1995 115 125
40. J.F. Scheid, H. Mouquet, N. Feldhahn, M.S. Seaman, K. Velinzon, J. Pietzsch, R.G. Ott, R.M. Anthony, H. Zebroski, and A. Hurley Broad diversity of neutralizing antibodies isolated from memory B cells in HIV-infected individuals Nature 458 2009 636 640
41. J.F. Scheid, H. Mouquet, N. Feldhahn, B.D. Walker, F. Pereyra, E. Cutrell, M.S. Seaman, J.R. Mascola, R.T. Wyatt, H. Wardemann, and M.C. Nussenzweig A method for identification of HIV gp140 binding memory B cells in human blood J. Immunol. Methods 343 2009 65 67
42. J.F. Scheid, H. Mouquet, B. Ueberheide, R. Diskin, F. Klein, T.Y. Oliveira, J. Pietzsch, D. Fenyo, A. Abadir, and K. Velinzon Sequence and structural convergence of broad and potent HIV antibodies that mimic CD4 binding Science 333 2011 1633 1637
43. M.S. Seaman, H. Janes, N. Hawkins, L.E. Grandpre, C. Devoy, A. Giri, R.T. Coffey, L. Harris, B. Wood, and M.G. Daniels Tiered categorization of a diverse panel of HIV-1 Env pseudoviruses for assessment of neutralizing antibodies J. Virol. 84 2010 1439 1452
44. R. Shibata, T. Igarashi, N. Haigwood, A. Buckler-White, R. Ogert, W. Ross, R. Willey, M.W. Cho, and M.A. Martin Neutralizing antibody directed against the HIV-1 envelope glycoprotein can completely block HIV-1/SIV chimeric virus infections of macaque monkeys Nat. Med. 5 1999 204 210 (Pubitemid 29068528)
45. M.D. Simek, W. Rida, F.H. Priddy, P. Pung, E. Carrow, D.S. Laufer, J.K. Lehrman, M. Boaz, T. Tarragona-Fiol, and G. Miiro Human immunodeficiency virus type 1 elite neutralizers: individuals with broad and potent neutralizing activity identified by using a high-throughput neutralization assay together with an analytical selection algorithm J. Virol. 83 2009 7337 7348
46. R.L. Stanfield, T.M. Fieser, R.A. Lerner, and I.A. Wilson Crystal structures of an antibody to a peptide and its complex with peptide antigen at 2.8 A Science 248 1990 712 719
47. M. Thali, J.P. Moore, C. Furman, M. Charles, D.D. Ho, J. Robinson, and J. Sodroski Characterization of conserved human immunodeficiency virus type 1 gp120 neutralization epitopes exposed upon gp120-CD4 binding J. Virol. 67 1993 3978 3988 (Pubitemid 23180722)
48. T. Tiller, M. Tsuiji, S. Yurasov, K. Velinzon, M.C. Nussenzweig, and H. Wardemann Autoreactivity in human IgG+ memory B cells Immunity 26 2007 205 213 (Pubitemid 46329436)
49. A. Trkola, M. Purtscher, T. Muster, C. Ballaun, A. Buchacher, N. Sullivan, K. Srinivasan, J. Sodroski, J.P. Moore, and H. Katinger Human monoclonal antibody 2G12 defines a distinctive neutralization epitope on the gp120 glycoprotein of human immunodeficiency virus type 1 J. Virol. 70 1996 1100 1108 (Pubitemid 26029030)
50. G.D. Victora, and M.C. Nussenzweig Germinal centers Annu. Rev. Immunol. 30 2012 429 457
51. S.D. Wagner, C. Milstein, and M.S. Neuberger Codon bias targets mutation Nature 376 1995 732
52. L.M. Walker, S.K. Phogat, P.Y. Chan-Hui, D. Wagner, P. Phung, J.L. Goss, T. Wrin, M.D. Simek, S. Fling, J.L. Mitcham Protocol G Principal Investigators Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target Science 326 2009 285 289
53. L.M. Walker, M. Huber, K.J. Doores, E. Falkowska, R. Pejchal, J.P. Julien, S.K. Wang, A. Ramos, P.Y. Chan-Hui, M. Moyle Protocol G Principal Investigators Broad neutralization coverage of HIV by multiple highly potent antibodies Nature 477 2011 466 470
54. L.M. Walker, D. Sok, Y. Nishimura, O. Donau, R. Sadjadpour, R. Gautam, M. Shingai, R. Pejchal, A. Ramos, and M.D. Simek Rapid development of glycan-specific, broad, and potent anti-HIV-1 gp120 neutralizing antibodies in an R5 SIV/HIV chimeric virus infected macaque Proc. Natl. Acad. Sci. USA 108 2011 20125 20129
55. X. Wei, J.M. Decker, S. Wang, H. Hui, J.C. Kappes, X. Wu, J.F. Salazar-Gonzalez, M.G. Salazar, J.M. Kilby, and M.S. Saag Antibody neutralization and escape by HIV-1 Nature 422 2003 307 312 (Pubitemid 36378357)
56. P.C. Wilson, O. de Bouteiller, Y.J. Liu, K. Potter, J. Banchereau, J.D. Capra, and V. Pascual Somatic hypermutation introduces insertions and deletions into immunoglobulin V genes J. Exp. Med. 187 1998 59 70 (Pubitemid 28044820)
57. T.T. Wu, and E.A. Kabat An analysis of the sequences of the variable regions of Bence Jones proteins and myeloma light chains and their implications for antibody complementarity J. Exp. Med. 132 1970 211 250
58. X. Wu, Z.Y. Yang, Y. Li, C.M. Hogerkorp, W.R. Schief, M.S. Seaman, T. Zhou, S.D. Schmidt, L. Wu, and L. Xu Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1 Science 329 2010 856 861
59. X. Wu, T. Zhou, J. Zhu, B. Zhang, I. Georgiev, C. Wang, X. Chen, N.S. Longo, M. Louder, K. McKee NISC Comparative Sequencing Program Focused evolution of HIV-1 neutralizing antibodies revealed by structures and deep sequencing Science 333 2011 1593 1602
60. X. Xiao, W. Chen, Y. Feng, and D.S. Dimitrov Maturation Pathways of Cross-Reactive HIV-1 Neutralizing Antibodies Viruses 1 2009 802 817
61. X. Xiao, W. Chen, Y. Feng, Z. Zhu, P. Prabakaran, Y. Wang, M.Y. Zhang, N.S. Longo, and D.S. Dimitrov Germline-like predecessors of broadly neutralizing antibodies lack measurable binding to HIV-1 envelope glycoproteins: implications for evasion of immune responses and design of vaccine immunogens Biochem. Biophys. Res. Commun. 390 2009 404 409
62. T. Zhou, I. Georgiev, X. Wu, Z.Y. Yang, K. Dai, A. Finzi, Y.D. Kwon, J.F. Scheid, W. Shi, and L. Xu Structural basis for broad and potent neutralization of HIV-1 by antibody VRC01 Science 329 2010 811 817
63. C.H. Bell, R. Pantophlet, A. Schiefner, L.A. Cavacini, R.L. Stanfield, D.R. Burton, and I.A. Wilson Structure of antibody F425-B4e8 in complex with a V3 peptide reveals a new binding mode for HIV-1 neutralization J. Mol. Biol. 375 2008 969 978 (Pubitemid 50010796)
64. V. Burke, C. Williams, M. Sukumaran, S.S. Kim, H. Li, X.H. Wang, M.K. Gorny, S. Zolla-Pazner, and X.P. Kong Structural basis of the cross-reactivity of genetically related human anti-HIV-1 mAbs: implications for design of V3-based immunogens Structure 17 2009 1538 1546
65. R.M. Cardoso, F.M. Brunel, S. Ferguson, M. Zwick, D.R. Burton, P.E. Dawson, and I.A. Wilson Structural basis of enhanced binding of extended and helically constrained peptide epitopes of the broadly neutralizing HIV-1 antibody 4E10 J. Mol. Biol. 365 2007 1533 1544 (Pubitemid 46048836)
66. L. Chen, Y.D. Kwon, T. Zhou, X. Wu, S. O'Dell, L. Cavacini, A.J. Hessell, M. Pancera, M. Tang, and L. Xu Structural basis of immune evasion at the site of CD4 attachment on HIV-1 gp120 Science 326 2009 1123 1127
67. R. Diskin, P.M. Marcovecchio, and P.J. Bjorkman Structure of a clade C HIV-1 gp120 bound to CD4 and CD4-induced antibody reveals anti-CD4 polyreactivity Nat. Struct. Mol. Biol. 17 2010 608 613
68. G.H. Gonnet, M.A. Cohen, and S.A. Benner Exhaustive matching of the entire protein sequence database Science 256 1992 1443 1445
69. C.C. Huang, M. Tang, M.Y. Zhang, S. Majeed, E. Montabana, R.L. Stanfield, D.S. Dimitrov, B. Korber, J. Sodroski, and I.A. Wilson Structure of a V3-containing HIV-1 gp120 core Science 310 2005 1025 1028 (Pubitemid 41611916)
70. C.C. Huang, S.N. Lam, P. Acharya, M. Tang, S.H. Xiang, S.S. Hussan, R.L. Stanfield, J. Robinson, J. Sodroski, and I.A. Wilson Structures of the CCR5 N terminus and of a tyrosine-sulfated antibody with HIV-1 gp120 and CD4 Science 317 2007 1930 1934 (Pubitemid 47509439)
71. S. Hubbard, and J. Thornton NACCESS. Computer Program 1993 Department of Biochemistry and Molecular Biology, University College London London
72. M.A. Luftig, M. Mattu, P. Di Giovine, R. Geleziunas, R. Hrin, G. Barbato, E. Bianchi, M.D. Miller, A. Pessi, and A. Carfí Structural basis for HIV-1 neutralization by a gp41 fusion intermediate-directed antibody Nat. Struct. Mol. Biol. 13 2006 740 747 (Pubitemid 44175168)
73. J.S. McLellan, M. Pancera, C. Carrico, J. Gorman, J.P. Julien, R. Khayat, R. Louder, R. Pejchal, M. Sastry, and K. Dai Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9 Nature 480 2011 336 343
74. G. Ofek, M. Tang, A. Sambor, H. Katinger, J.R. Mascola, R. Wyatt, and P.D. Kwong Structure and mechanistic analysis of the anti-human immunodeficiency virus type 1 antibody 2F5 in complex with its gp41 epitope J. Virol. 78 2004 10724 10737 (Pubitemid 39258398)
75. M. Pancera, S. Majeed, Y.E. Ban, L. Chen, C.C. Huang, L. Kong, Y.D. Kwon, J. Stuckey, T. Zhou, and J.E. Robinson Structure of HIV-1 gp120 with gp41-interactive region reveals layered envelope architecture and basis of conformational mobility Proc. Natl. Acad. Sci. USA 107 2010 1166 1171
76. R.L. Stanfield, M.K. Gorny, C. Williams, S. Zolla-Pazner, and I.A. Wilson Structural rationale for the broad neutralization of HIV-1 by human monoclonal antibody 447-52D Structure 12 2004 193 204 (Pubitemid 38224543)
77. R.L. Stanfield, M.K. Gorny, S. Zolla-Pazner, and I.A. Wilson Crystal structures of human immunodeficiency virus type 1 (HIV-1) neutralizing antibody 2219 in complex with three different V3 peptides reveal a new binding mode for HIV-1 cross-reactivity J. Virol. 80 2006 6093 6105 (Pubitemid 43849187)
78. T. Zhou, L. Xu, B. Dey, A.J. Hessell, D. Van Ryk, S.H. Xiang, X. Yang, M.Y. Zhang, M.B. Zwick, and J. Arthos Structural definition of a conserved neutralization epitope on HIV-1 gp120 Nature 445 2007 732 737 (Pubitemid 46279718)