The HIV-1 envelope glycoprotein structure: nailing down a moving target

Immunological Reviews

Volumn 275, Issue 1, 2017, Pages 21-32

  Ward, Andrew B ^a   Wilson, Ian A ^a,b  

^a International AIDS Vaccine Initiative Neutralizing Antibody Center   (United States)

^b SCRIPPS RESEARCH INSTITUTE   (United States)

Author keywords

cryo electron microscopy; epitope mapping; glycan shield; HIV envelope structure; structure based vaccine design; x ray crystallography

Indexed keywords

EPITOPE; HUMAN IMMUNODEFICIENCY VIRUS ANTIGEN; HUMAN IMMUNODEFICIENCY VIRUS VACCINE; NEUTRALIZING ANTIBODY; VIRUS ENVELOPE PROTEIN; HUMAN IMMUNODEFICIENCY VIRUS ANTIBODY;

CARBOXY TERMINAL SEQUENCE; CLADISTICS; CRYOELECTRON MICROSCOPY; CRYSTAL STRUCTURE; EPITOPE MAPPING; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; NEXT GENERATION SEQUENCING; NONHUMAN; PRIORITY JOURNAL; PROTEIN STRUCTURE; REVIEW; VIRUS MUTATION; VIRUS NEUTRALIZATION; X RAY CRYSTALLOGRAPHY; ANIMAL; CHEMISTRY; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMMUNOLOGY; METABOLISM; PROTEIN CONFORMATION;

AIDS VACCINES; ANIMALS; ANTIBODIES, NEUTRALIZING; CRYSTALLOGRAPHY, X-RAY; EPITOPES; HIV ANTIBODIES; HIV ANTIGENS; HIV INFECTIONS; HIV-1; HUMANS; PROTEIN CONFORMATION; VIRAL ENVELOPE PROTEINS;

EID: 85010843666     PISSN: 01052896     EISSN: 1600065X     Source Type: Journal    
DOI: 10.1111/imr.12507     Document Type: Review

References (98)

1. Brand CM, Skehel JJ. Crystalline antigen from the influenza virus envelope. Nat New Biol. 1972;238:145–147.
2. Wiley DC, Skehel JJ. Crystallization and x-ray diffraction studies on the haemagglutinin glycoprotein from the membrane of influenza virus. J Mol Biol. 1977;112:343–347.
3. Wrigley NG, Laver WG, Downie JC. Binding of antibodies to isolated haemagglutinin and neuraminidase molecules of influenza virus observed in the electron microscope. J Mol Biol. 1977;109:405–421.
4. Laver WG, Valentine RC. Morphology of the isolated hemagglutinin and neuraminidase subunits of influenza virus. Virology. 1969;38:105–119.
5. Wrigley NG, Skehel JJ, Charlwood PA, Brand CM. The size and shape of influenza virus neuraminidase. Virology. 1973;51:525–529.
6. Wilson IA, Skehel JJ, Wiley DC. Structure of the haemagglutinin membrane glycoprotein of influenza virus at 3 Å resolution. Nature. 1981;289:366–373.
7. Varghese JN, Laver WG, Colman PM. Structure of the influenza virus glycoprotein antigen neuraminidase at 2.9 Å resolution. Nature. 1983;303:35–40.
8. Stevens J, Corper AL, Basler CF, Taubenberger JK, Palese P, Wilson IA. Structure of the uncleaved human H1 hemagglutinin from the extinct 1918 influenza virus. Science. 2004;303:1866–1870.
9. Binley JM, Sanders RW, Clas B, et al. 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. 2000;74:627–643.
10. Sanders RW, Schiffner L, Master A, et al. Variable-loop-deleted variants of the human immunodeficiency virus type 1 envelope glycoprotein can be stabilized by an intermolecular disulfide bond between the gp120 and gp41 subunits. J Virol. 2000;74:5091–5100.
11. Sanders RW, Vesanen M, Schuelke N, et al. Stabilization of the soluble, cleaved, trimeric form of the envelope glycoprotein complex of human immunodeficiency virus type 1. J Virol. 2002;76:8875–8889.
12. Sanders RW, Moore JP. Native-like ENV trimers as a platform for HIV-1 vaccine design. Immunol Rev. 2017;275:161–182.
13. Lyumkis D, Julien JP, de Val N, et al. Cryo-EM structure of a fully glycosylated soluble cleaved HIV-1 envelope trimer. Science. 2013;342:1484–1490.
14. Julien JP, Cupo A, Sok D, et al. Crystal structure of a soluble cleaved HIV-1 envelope trimer. Science. 2013;342:1477–1483.
15. Yin HS, Wen X, Paterson RG, Lamb RA, Jardetzky TS. Structure of the parainfluenza virus 5 F protein in its metastable, prefusion conformation. Nature. 2006;439:38–44.
16. Roche S, Rey FA, Gaudin Y, Bressanelli S. Structure of the prefusion form of the vesicular stomatitis virus glycoprotein G. Science. 2007;315:843–848.
17. McLellan JS, Yang Y, Graham BS, Kwong PD. Structure of respiratory syncytial virus fusion glycoprotein in the postfusion conformation reveals preservation of neutralizing epitopes. J Virol. 2011;85:7788–7796.
18. McLellan JS, Chen M, Leung S, et al. Structure of RSV fusion glycoprotein trimer bound to a prefusion-specific neutralizing antibody. Science. 2013;340:1113–1117.
19. Lee JE, Fusco ML, Hessell AJ, Oswald WB, Burton DR, Saphire EO. Structure of the Ebola virus glycoprotein bound to an antibody from a human survivor. Nature. 2008;454:177–182.
20. Pallesen J, Murin CD, del Val N, et al. Structures of Ebola virus GP and sGP in complex with therapeutic antibodies. Nat Microbiol. 2016;1:16128.
21. Zhao Y, Ren J, Harlos K, et al. Toremifene interacts with and destabilizes the Ebola virus glycoprotein. Nature. 2016;535:169–172.
22. Kong L, Giang E, Nieusma T, et al. Hepatitis C virus E2 envelope glycoprotein core structure. Science. 2013;342:1090–1094.
23. Khan AG, Whidby J, Miller MT, et al. Structure of the core ectodomain of the hepatitis C virus envelope glycoprotein 2. Nature. 2014;509:381–384.
24. Kirchdoerfer RN, Cottrell CA, Wang N, et al. Pre-fusion structure of a human coronavirus spike protein. Nature. 2016;531:118–121.
25. Hastie KM, Igonet S, Sullivan BM, et al. Crystal structure of the prefusion surface glycoprotein of the prototypic arenavirus LCMV. Nat Struct Mol Biol. 2016;23:513–521.
26. Zeev-Ben-Mordehai T, Vasishtan D, Hernandez Duran A, et al. Two distinct trimeric conformations of natively membrane-anchored full-length herpes simplex virus 1 glycoprotein B. Proc Natl Acad Sci USA. 2016;113:4176–4181.
27. Halldorsson S, Behrens AJ, Harlos K, et al. Structure of a phleboviral envelope glycoprotein reveals a consolidated model of membrane fusion. Proc Natl Acad Sci USA. 2016;113:7154–7159.
28. Li S, Rissanen I, Zeltina A, et al. A molecular-mevel account of the antigenic hantaviral surface. Cell Rep. 2016;15:959–967.
29. Bakkers MJ, Zeng Q, Feitsma LJ, et al. Coronavirus receptor switch explained from the stereochemistry of protein-carbohydrate interactions and a single mutation. Proc Natl Acad Sci USA. 2016;113:E3111–E3119.
30. Chan DC, Fass D, Berger JM, Kim PS. Core structure of gp41 from the HIV envelope glycoprotein. Cell. 1997;89:263–273.
31. Weissenhorn W, Dessen A, Harrison SC, Skehel JJ, Wiley DC. Atomic structure of the ectodomain from HIV-1 gp41. Nature. 1997;387:426–430.
32. Tan K, Liu J, Wang J, Shen S, Lu M. Atomic structure of a thermostable subdomain of HIV-1 gp41. Proc Natl Acad Sci USA. 1997;94:12303–12308.
33. Kwong PD, Wyatt R, Robinson J, Sweet RW, Sodroski J, Hendrickson WA. Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody. Nature. 1998;393:648–659.
34. Huang CC, Lam SN, Acharya P, et al. Structures of the CCR5 N terminus and of a tyrosine-sulfated antibody with HIV-1 gp120 and CD4. Science. 2007;317:1930–1934.
35. Pancera M, Majeed S, Ban YE, 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.
36. Kwon YD, Finzi A, Wu X, et al. Unliganded HIV-1 gp120 core structures assume the CD4-bound conformation with regulation by quaternary interactions and variable loops. Proc Natl Acad Sci USA. 2012;109:5663–5668.
37. Zhu P, Chertova E, Bess J, Jr, et al. Electron tomography analysis of envelope glycoprotein trimers on HIV and simian immunodeficiency virus virions. Proc Natl Acad Sci USA. 2003;100:15812–15817.
38. Zhu P, Liu J, Bess J, Jr, et al. Distribution and three-dimensional structure of AIDS virus envelope spikes. Nature. 2006;441:847–852.
39. Zanetti G, Briggs JA, Grunewald K, Sattentau QJ, Fuller SD. Cryo-electron tomographic structure of an immunodeficiency virus envelope complex in situ. PLoS Pathog. 2006;2:e83.
40. Liu J, Bartesaghi A, Borgnia MJ, Sapiro G, Subramaniam S. Molecular architecture of native HIV-1 gp120 trimers. Nature. 2008;455:109–113.
41. Tran EE, Borgnia MJ, Kuybeda O, et al. Structural mechanism of trimeric HIV-1 envelope glycoprotein activation. PLoS Pathog. 2012;8:e1002797.
42. Bartesaghi A, Merk A, Borgnia MJ, Milne JL, Subramaniam S. Prefusion structure of trimeric HIV-1 envelope glycoprotein determined by cryo-electron microscopy. Nat Struct Mol Biol. 2013;20:1352–1357.
43. Khayat R, Lee JH, Julien JP, et al. Structural characterization of cleaved, soluble HIV-1 envelope glycoprotein trimers. J Virol. 2013;87:9865–9872.
44. Klasse PJ, Depetris RS, Pejchal R, et al. Influences on trimerization and aggregation of soluble, cleaved HIV-1 SOSIP envelope glycoprotein. J Virol. 2013;87:9873–9885.
45. Julien JP, Lee JH, Cupo A, et al. Asymmetric recognition of the HIV-1 trimer by broadly neutralizing antibody PG9. Proc Natl Acad Sci USA. 2013;110:4351–4356.
46. Sanders RW, Derking R, Cupo A, et al. A next-generation cleaved, soluble HIV-1 Env trimer, BG505 SOSIP.664 gp140, expresses multiple epitopes for broadly neutralizing but not non-neutralizing antibodies. PLoS Pathog. 2013;9:e1003618.
47. Ringe RP, Sanders RW, Yasmeen A, et al. Cleavage strongly influences whether soluble HIV-1 envelope glycoprotein trimers adopt a native-like conformation. Proc Natl Acad Sci USA. 2013;110:18256–18261.
48. McCoy LE, Burton DR. Identification and specificity of broadly neutralizing antibodies against HIV. Immunol Rev. 2017;275:11–20.
49. Walker LM, Phogat SK, Chan-Hui PY, et al. Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target. Science. 2009;326:285–289.
50. Doria-Rose NA, Schramm CA, Gorman J, et al. Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies. Nature. 2014;509:55–62.
51. Scheid JF, Mouquet H, Feldhahn N, et al. A method for identification of HIV gp140 binding memory B cells in human blood. J Immunol Methods. 2009;343:65–67.
52. Scheid JF, Mouquet H, Feldhahn N, et al. Broad diversity of neutralizing antibodies isolated from memory B cells in HIV-infected individuals. Nature. 2009;458:636–640.
53. Doria-Rose NA, Bhiman JN, Roark RS, et al. New member of the V1V2-directed CAP256-VRC26 lineage that shows increased breadth and exceptional potency. J Virol. 2016;90:76–91.
54. Sok D, van Gils MJ, Pauthner M, et al. Recombinant HIV envelope trimer selects for quaternary-dependent antibodies targeting the trimer apex. Proc Natl Acad Sci USA. 2014;111:17624–17629.
55. Kong L, Lee JH, Doores KJ, et al. Supersite of immune vulnerability on the glycosylated face of HIV-1 envelope glycoprotein gp120. Nat Struct Mol Biol. 2013;20:796–803.
56. Li X, Mooney P, Zheng S, et al. Electron counting and beam-induced motion correction enable near-atomic-resolution single-particle cryo-EM. Nat Methods. 2013;10:584–590.
57. Tran K, Poulsen C, Guenaga J, et al. Vaccine-elicited primate antibodies use a distinct approach to the HIV-1 primary receptor binding site informing vaccine redesign. Proc Natl Acad Sci USA. 2014;111:E738–E747.
58. Ward AB, Wilson IA. Insights into the trimeric HIV-1 envelope glycoprotein structure. Trends Biochem Sci. 2015;40:101–107.
59. Pancera M, Zhou T, Druz A, et al. Structure and immune recognition of trimeric pre-fusion HIV-1 Env. Nature. 2014;514:455–461.
60. Jardine JG, Sok D, Julien J.-P, et al. Minimally mutated HIV-1 broadly neutralizing antibodies to guide reductionist vaccine design. PLoS Pathog. 2016;12:e1005815.
61. Kong L, Torrents de la Pena A, Deller MC, et al. Complete epitopes for vaccine design derived from a crystal structure of the broadly neutralizing antibodies PGT128 and 8ANC195 in complex with an HIV-1 Env trimer. Acta Crystallogr D Biol Crystallogr. 2015;71:2099–2108.
62. Scharf L, Wang H, Gao H, Chen S, McDowall AW, Bjorkman PJ. Broadly neutralizing antibody 8ANC195 recognizes closed and open states of HIV-1 Env. Cell. 2015;162:1379–1390.
63. Garces F, Lee JH, de Val N, et al. Affinity maturation of a potent family of HIV antibodies is primarily focused on accommodating or avoiding glycans. Immunity. 2015;43:1053–1063.
64. Garces F, Sok D, Kong L, et al. Structural evolution of glycan recognition by a family of potent HIV antibodies. Cell. 2014;159:69–79.
65. Pejchal R, Doores KJ, Walker LM, et al. A potent and broad neutralizing antibody recognizes and penetrates the HIV glycan shield. Science. 2011;334:1097–1103.
66. McLellan JS, Pancera M, Carrico C, et al. Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9. Nature. 2011;480:336–343.
67. Stewart-Jones GB, Soto C, Lemmin T, et al. Trimeric HIV-1-Env structures define glycan shields from Clades A, B, and G. Cell. 2016;165:813–826.
68. Schief WR, Ban YE, Stamatatos L. Challenges for structure-based HIV vaccine design. Curr Opin HIV AIDS. 2009;4:431–440.
69. Lee JH, Ozorowski G, Ward AB. Cryo-EM structure of a native, fully glycosylated, cleaved HIV-1 envelope trimer. Science. 2016;351:1043–1048.
70. Lee JH, de Val N, Lyumkis D, Ward AB. Model building and refinement of a natively glycosylated HIV-1 Env protein by high-resolution cryoelectron microscopy. Structure. 2015;23:1943–1951.
71. Behrens AJ, Vasiljevic S, Pritchard LK, et al. Composition and antigenic effects of individual glycan sites of a trimeric HIV-1 envelope glycoprotein. Cell Rep. 2016;14:2695–2706.
72. Pritchard LK, Spencer DI, Royle L, et al. Glycan clustering stabilizes the mannose patch of HIV-1 and preserves vulnerability to broadly neutralizing antibodies. Nat Commun. 2015;6:7479.
73. Pritchard LK, Vasiljevic S, Ozorowski G, et al. Structural constraints determine the glycosylation of HIV-1 envelope trimers. Cell Rep. 2015;11:1604–1613.
74. Dwek RA, Ashford DA, Edge CJ, et al. Glycosylation of CD4 and Thy-1. Philos Trans R Soc Lond B Biol Sci. 1993;342:43–50.
75. Bonomelli C, Doores KJ, Dunlop DC, et al. The glycan shield of HIV is predominantly oligomannose independently of production system or viral clade. PLoS ONE. 2011;6:e23521.
76. Doores KJ, Bonomelli C, Harvey DJ, et al. Envelope glycans of immunodeficiency virions are almost entirely oligomannose antigens. Proc Natl Acad Sci USA. 2010;107:13800–13805.
77. Go EP, Herschhorn A, Gu C, et al. Comparative analysis of the glycosylation profiles of membrane-anchored HIV-1 envelope glycoprotein trimers and soluble gp140. J Virol. 2015;89:8245–8257.
78. Go EP, Cupo A, Ringe R, Pugach P, Moore JP, Desaire H. Native conformation and canonical disulfide bond formation are interlinked properties of HIV-1 Env glycoproteins. J Virol. 2016;90:2884–2894.
79. Ringe RP, Yasmeen A, Ozorowski G, et al. Influences on the design and purification of soluble, recombinant native-like HIV-1 envelope glycoprotein trimers. J Virol. 2015;89:12189–12210.
80. Pugach P, Ozorowski G, Cupo A, et al. A native-like SOSIP.664 trimer based on an HIV-1 subtype B env gene. J Virol. 2015;89:3380–3395.
81. Julien JP, Lee JH, Ozorowski G, et al. Design and structure of two HIV-1 clade C SOSIP.664 trimers that increase the arsenal of native-like Env immunogens. Proc Natl Acad Sci USA. 2015;112:11947–11952.
82. Sanders RW, van Gils MJ, Derking R, et al. HIV-1 neutralizing antibodies induced by native-like envelope trimers. Science. 2015;349:aac4223.
83. Yasmeen A, Ringe R, Derking R, et al. Differential binding of neutralizing and non-neutralizing antibodies to native-like soluble HIV-1 Env trimers, uncleaved Env proteins, and monomeric subunits. Retrovirology. 2014;11:41.
84. Sharma SK, de Val N, Bale S, et al. Cleavage-independent HIV-1 Env trimers engineered as soluble native spike mimetics for vaccine design. Cell Rep. 2015;11:539–550.
85. Guenaga J, Dubrovskaya V, de Val N, et al. Structure-guided redesign increases the propensity of HIV Env to generate highly stable soluble trimers. J Virol. 2016;90:2806–2817.
86. Georgiev IS, Joyce MG, Yang Y, et al. Single-chain soluble BG505.SOSIP gp140 trimers as structural and antigenic mimics of mature closed HIV-1 Env. J Virol. 2015;89:5318–5329.
87. de Taeye SW, Ozorowski G, Torrents de la Pena A, et al. Immunogenicity of stabilized HIV-1 envelope trimers with reduced exposure of non-neutralizing epitopes. Cell. 2015;163:1702–1715.
88. Kong L, He L, de Val N, et al. Uncleaved prefusion-optimized gp140 trimers derived from analysis of HIV-1 envelope metastability. Nat Commun. 2016;7:12040.
89. Munro JB, Gorman J, Ma X, et al. Conformational dynamics of single HIV-1 envelope trimers on the surface of native virions. Science. 2014;346:759–763.
90. Munro JB, Mothes W. Structure and dynamics of the native HIV-1 Env trimer. J Virol. 2015;89:5752–5755.
91. Blattner C, Lee JH, Sliepen K, et al. Structural delineation of a quaternary, cleavage-dependent epitope at the gp41-gp120 interface on intact HIV-1 Env trimers. Immunity. 2014;40:669–680.
92. Kong R, Xu K, Zhou T, et al. Fusion peptide of HIV-1 as a site of vulnerability to neutralizing antibody. Science. 2016;352:828–833.
93. McCoy LE, van Gils MJ, Ozorowski G, et al. Holes in the glycan shield of the native HIV envelope are a target of trimer-elicited neutralizing antibodies. Cell Rep. 2016;16:2327–2338.
94. Lee PS, Wilson IA. Structural characterization of viral epitopes recognized by broadly cross-reactive antibodies. Curr Top Microbiol Immunol. 2015;386:323–341.
95. Julien JP, Lee PS, Wilson IA. Structural insights into key sites of vulnerability on HIV-1 Env and influenza HA. Immunol Rev. 2012;250:180–198.
96. Burton DR, Mascola JR. Antibody responses to envelope glycoproteins in HIV-1 infection. Nat Immunol. 2015;16:571–576.
97. Julien JP, Sok D, Khayat R, et al. Broadly neutralizing antibody PGT121 allosterically modulates CD4 binding via recognition of the HIV-1 gp120 V3 base and multiple surrounding glycans. PLoS Pathog. 2013;9:e1003342.
98. Elsliger MA, Deacon AM, Godzik A, et al. The JCSG high-throughput structural biology pipeline. Acta Crystallogr F Struct Biol Cryst Commun. 2010;66:1137–1142.