Trimeric HIV Env provides epitope occlusion mediated by hypervariable loops

Scientific Reports

Volumn 4, Issue , 2014, Pages

  Moscoso, Carlos G ^a   Xing, Li ^a   Hui, Jinwen ^a   Hu, Jeffrey ^a   Kalkhoran, Mohammad Baikoghli ^a   Yenigun, Onur M ^a   Sun, Yide ^b   Paavolainen, Lassi ^c   Martin, Loïc ^d   Vahlne, Anders ^e   Zambonelli, Carlo ^b,f   Barnett, Susan W ^b   Srivastava, Indresh K ^b,g   Cheng, R Holland ^a,e  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b Novartis Vaccines and Diagnostics Inc   (United States)

^c UNIVERSITY OF JYVÄSKYLÄ   (Finland)

^d SERVICE DE CHIMIE BIOORGANIQUE ET DE MARQUAGE   (France)

^e KAROLINSKA INSTITUTE   (Sweden)

^f NOVARTIS VACCINES AND DIAGNOSTICS   (Italy)

^g Protein Sciences Corp   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CD4 ANTIGEN; EPITOPE; GLYCOPROTEIN GP 120; GLYCOPROTEIN GP 41; PEPTIDE FRAGMENT; PROTEIN BINDING; VIRUS ENVELOPE PROTEIN;

CHEMICAL STRUCTURE; CHEMISTRY; GENE DELETION; GENETICS; HUMAN; METABOLISM; PROTEIN CONFORMATION; PROTEIN DOMAIN; PROTEIN MULTIMERIZATION;

ANTIGENS, CD4; ENV GENE PRODUCTS, HUMAN IMMUNODEFICIENCY VIRUS; EPITOPES; HIV ENVELOPE PROTEIN GP120; HIV ENVELOPE PROTEIN GP41; HUMANS; MODELS, MOLECULAR; PEPTIDE FRAGMENTS; PROTEIN BINDING; PROTEIN CONFORMATION; PROTEIN INTERACTION DOMAINS AND MOTIFS; PROTEIN MULTIMERIZATION; SEQUENCE DELETION;

EID: 84923154104     PISSN: None     EISSN: 20452322     Source Type: Journal    
DOI: 10.1038/srep07025     Document Type: Article

References (66)

1. Lifson, J., Coutre, S., Huang, E. & Engleman, E. Role of envelope glycoprotein carbohydrate in human immunodeficiency virus (HIV) infectivity and virusinduced cell fusion. J Exp Med 164, 2101-2106 (1986).
2. Pinter, A. et al. Oligomeric structure of gp41, the transmembrane protein of human immunodeficiency virus type 1. J Virol 63, 2674-2679 (1989).
3. Moscoso, C. G. et al. Quaternary structures of HIV Env immunogen exhibit conformational vicissitudes and interface diminution elicited by ligand binding. Proc Natl Acad Sci U S A 108, 6091-6096, doi:10.1073/pnas.1016113108 (2011).
4. Stamatatos, L., Wiskerchen, M. & Cheng-Mayer, C. Effect of major deletions in the V1 and V2 loops of a macrophage-tropic HIV type 1 isolate on viral envelope structure, cell entry, and replication. AIDS ResHum Retrov 14, 1129-1139 (1998).
5. Barnett, S. W. et al. The ability of an oligomeric human immunodeficiency virus type 1 (HIV-1) envelope antigen to elicit neutralizing antibodies against primary HIV-1 isolates is improved following partial deletion of the second hypervariable region. J Virol 75, 5526-5540, doi:10.1128/JVI.75.12.5526-5540.2001 (2001).
6. Srivastava, I. K., VanDorsten, K., Vojtech, L., Barnett, S. W. & Stamatatos, L. Changes in the immunogenic properties of soluble gp140 human immunodeficiency virus envelope constructs upon partial deletion of the second hypervariable region. J Virol 77, 2310-2320 (2003).
7. Harris, A. et al. Trimeric HIV-1 glycoprotein gp140 immunogens and native HIV- 1 envelope glycoproteins display the same closed and open quaternary molecular architectures. Proc Natl Acad Sci U S A, doi:10.1073/pnas.1101414108 (2011).
8. Changela, A. et al. Crystal structure of human antibody 2909 reveals conserved features of quaternary structure-specific antibodies that potently neutralize HIV-1. J Virol 85, 2524-2535, doi:10.1128/JVI.02335-10 (2011).
9. Tran, E. E. et al. Structural mechanism of trimeric HIV-1 envelope glycoprotein activation. PLoS Pathog 8, e1002797, doi:10.1371/journal.ppat.1002797 (2012).
10. Wu, S. R. et al. Single-particle cryoelectron microscopy analysis reveals the HIV-1 spike as a tripod structure. Proc Natl Acad Sci U S A 107, 18844-18849, doi:10.1073/pnas.1007227107 (2010).
11. Mao, Y. et al. Subunit organization of the membrane-bound HIV-1 envelope glycoprotein trimer. Nat Struct Mol Biol 19, 893-899, doi:10.1038/nsmb.2351 (2012).
12. Mao, Y. et al. Molecular architecture of the uncleaved HIV-1 envelope glycoprotein trimer. Proc Natl Acad Sci U S A 110, 12438-12443, doi:10.1073/ pnas.1307382110 (2013).
13. 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 65, 2119-2123 (1991).
14. Jacobs, A., Sen, J., Rong, L. & Caffrey, M. Alanine scanning mutants of the HIV gp41 loop. J Biol Chem 280, 27284-27288, doi:10.1074/jbc.M414411200 (2005).
15. Sen, J., Jacobs, A. & Caffrey, M. Role of the HIV gp120 conserved domain 5 in processing and viral entry. Biochemistry 47, 7788-7795, doi:10.1021/bi800227z (2008).
16. Poumbourios, P., Maerz, A. L. & Drummer, H. E. Functional evolution of the HIV-1 envelope glycoprotein 120 association site of glycoprotein 41. J Biol Chem 278, 42149-42160, doi:10.1074/jbc.M305223200 (2003).
17. Wang, J., Sen, J., Rong, L. & Caffrey, M. Role of the HIV gp120 conserved domain 1 in processing and viral entry. J Biol Chem 283, 32644-32649, doi:10.1074/ jbc.M806099200 (2008).
18. Wyatt, R. et al. Analysis of the interaction of the human immunodeficiency virus type 1 gp120 envelope glycoprotein with the gp41 transmembrane glycoprotein. J Virol 71, 9722-9731 (1997).
19. York, J. & Nunberg, J. H. Role of hydrophobic residues in the central ectodomain of gp41 in maintaining the association between human immunodeficiency virus type 1 envelope glycoprotein subunits gp120 and gp41. J Virol 78, 4921-4926 (2004).
20. Lyumkis, D. et al. Cryo-EM structure of a fully glycosylated soluble cleaved HIV-1 envelope trimer. Science 342, 1484-1490, doi:10.1126/science.1245627 (2013).
21. Julien, J. P. et al. Crystal structure of a soluble cleaved HIV-1 envelope trimer. Science 342, 1477-1483, doi:10.1126/science.1245625 (2013).
22. Bartesaghi, A., Merk, A., Borgnia, M. J., Milne, J. L. & Subramaniam, S. Prefusion structure of trimeric HIV-1 envelope glycoprotein determined by cryo-electron microscopy. Nat Struct Mol Biol 20, 1352-1357, doi:10.1038/nsmb.2711 (2013).
23. Kovacs, J. M. et al. HIV-1 envelope trimer elicits more potent neutralizing antibody responses than monomeric gp120. Proc Natl Acad Sci U S A, doi:10.1073/pnas.1204533109 (2012).
24. Walker, L. M. et al. Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target. Science 326, 285-289, doi:10.1126/ science.1178746 (2009).
25. Sanders, R. W. 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 74, 5091-5100 (2000).
26. Wan, Y. et al. Deglycosylation or partial removal of HIV-1 CN54 gp140 V1/V2 domain enhances env-specific T cells. AIDS Res Hum Retrov 25, 607-617, doi:10.1089/aid.2008.0289 (2009).
27. Cao, J. et al. Replication and neutralization of human immunodeficiency virus type 1 lacking the V1 and V2 variable loops of the gp120 envelope glycoprotein. J Virol 71, 9808-9812 (1997).
28. Kim, Y. B., Han, D. P., Cao, C. & Cho, M. W. Immunogenicity and ability of variable loop-deleted human immunodeficiency virus type 1 envelope glycoproteins to elicit neutralizing antibodies. Virology 305, 124-137 (2003).
29. Bar, K. J. et al. Early low-titer neutralizing antibodies impede HIV-1 replication and select for virus escape. PLoS Pathog 8, e1002721, doi:10.1371/ journal.ppat.1002721 (2012).
30. Harrington, P. R., Nelson, J. A., Kitrinos, K. M. & Swanstrom, R. Independent evolution of human immunodeficiency virus type 1 env V1/V2 and V4/V5 hypervariable regions during chronic infection. J Virol 81, 5413-5417, doi:10.1128/JVI.02554-06 (2007).
31. Liang, X. et al. Epitope insertion into variable loops of HIV-1 gp120 as a potential means to improve immunogenicity of viral envelope protein. Vaccine 17, 2862-2872 (1999).
32. Johnson, W. E. et al. A replication-competent, neutralization-sensitive variant of simian immunodeficiency virus lacking 100 amino acids of envelope. J Virol 76, 2075-2086 (2002).
33. Srivastava, I. K. et al. Purification, characterization, and immunogenicity of a soluble trimeric envelope protein containing a partial deletion of the V2 loop derived from SF162, an R5-tropic human immunodeficiency virus type 1 isolate. J Virol 77, 11244-11259 (2003).
34. Srivastava, I. K. et al. Comparative evaluation of trimeric envelope glycoproteins derived from subtype C and B HIV-1 R5 isolates. Virology 372, 273-290, doi:10.1016/j.virol.2007.10.022 (2008).
35. Stamatatos, L. & Cheng-Mayer, C. An envelope modification that renders a primary, neutralization-resistant clade B human immunodeficiency virus type 1 isolate highly susceptible to neutralization by sera from other clades. J Virol 72, 7840-7845 (1998).
36. Utachee, P. et al. Two N-linked glycosylation sites in the V2 and C2 regions of human immunodeficiency virus type 1 CRF01-AE envelope glycoprotein gp120 regulate viral neutralization susceptibility to the human monoclonal antibody specific for the CD4 binding domain. J Virol 84, 4311-4320, doi:10.1128/ JVI.02619-09 (2010).
37. Poon, S. et al. Putative role of Tat-Env interaction in HIV infection. AIDS, doi:10.1097/01.aids.0000432453.60733.b2 (2013).
38. Rong, R. et al. Role of V1V2 and other human immunodeficiency virus type 1 envelope domains in resistance to autologous neutralization during clade C infection. J Virol 81, 1350-1359, doi:10.1128/JVI.01839-06 (2007).
39. Gorny, M. K. et al. Identification of a new quaternary neutralizing epitope on human immunodeficiency virus type 1 virus particles. J Virol 79, 5232-5237, doi:10.1128/JVI.79.8.5232-5237.2005 (2005).
40. Pancera, M. et al. Crystal Structure of PG16 and Chimeric Dissection with Somatically Related PG9: Structure-Function Analysis of Two Quaternary- Specific Antibodies That Effectively Neutralize HIV-1. J Virol 84, 8098-8110, doi:10.1128/JVI.00966-10 (2010).
41. Zanetti, G., Briggs, J. A., Grunewald, K., Sattentau, Q. J. & Fuller, S. D. Cryoelectron tomographic structure of an immunodeficiency virus envelope complex in situ. PLoS Pathog 2, e83 (2006).
42. Zhu, P. et al.Distribution and three-dimensional structure of AIDS virus envelope spikes. Nature 441, 847-852, doi:10.1038/nature04817 (2006).
43. Liu, J., Bartesaghi, A., Borgnia, M. J., Sapiro, G. & Subramaniam, S. Molecular architecture of native HIV-1 gp120 trimers. Nature 455, 109-113, doi:10.1038/ nature07159 (2008).
44. Zhu, P., Winkler, H., Chertova, E., Taylor, K. A. & Roux, K. H. Cryoelectron tomography of HIV-1 envelope spikes: further evidence for tripod-like legs. PLoS Pathog 4, e1000203, doi:10.1371/journal.ppat.1000203 (2008).
45. White, T. A. et al. Molecular architectures of trimeric SIV and HIV-1 envelope glycoproteins on intact viruses: strain-dependent variation in quaternary structure. PLoS Pathog 6, e1001249, doi:10.1371/journal.ppat.1001249 (2010).
46. Chen, B. et al. Structure of an unliganded simian immunodeficiency virus gp120 core. Nature 433, 834-841 (2005).
47. White, T. A. et al. Three-Dimensional Structures of Soluble CD4-Bound States of Trimeric Simian Immunodeficiency Virus Envelope Glycoproteins Determined by Using Cryo-Electron Tomography. J Virol 85, 12114-12123, doi:10.1128/ JVI.05297-11 (2011).
48. VanHerrewege, Y. et al. CD4 mimetic miniproteins: potent anti-HIV compounds with promising activity as microbicides. J Antimicrob Chemoth 61, 818-826, doi:10.1093/jac/dkn042 (2008).
49. Sjoberg, M. et al. Furin cleavage of the Moloney murine leukemia virus Env precursor reorganizes the spike structure. Proc Natl Acad Sci U S A, doi:10.1073/ pnas.1317972111 (2014).
50. Huang, C. C. et al. Structure of a V3-containing HIV-1 gp120 core. Science 310, 1025-1028, doi:10.1126/science.1118398 (2005).
51. Davenport, T. M. et al. Binding interactions between soluble HIV envelope glycoproteins and quaternary-structure-specific MAbs PG9 and PG16. J Virol, doi:10.1128/JVI.00411-11 (2011).
52. Pinter, A. et al. The V1/V2 domain of gp120 is a global regulator of the sensitivity of primary human immunodeficiency virus type 1 isolates to neutralization by antibodies commonly induced upon infection. J Virol 78, 5205-5215 (2004).
53. Werner, A. & Levy, J. A. Human immunodeficiency virus type 1 envelope gp120 is cleaved after incubation with recombinant soluble CD4. J Virol 67, 2566-2574 (1993).
54. Li, Y. et al. Removal of a single N-linked glycan in human immunodeficiency virus type 1 gp120 results in an enhanced ability to induce neutralizing antibody responses. J Virol 82, 638-651, doi:10.1128/JVI.01691-07 (2008).
55. Stamatatos, L., Lim, M. & Cheng-Mayer, C. Generation and structural analysis of soluble oligomeric gp140 envelope proteins derived from neutralization-resistant and neutralization-susceptible primary HIV type 1 isolates. AIDS ResHum Retrov 16, 981-994, doi:10.1089/08892220050058407 (2000).
56. Moore, P. L. et al. The c3-v4 region is a major target of autologous neutralizing antibodies in human immunodeficiency virus type 1 subtype C infection. J Virol 82, 1860-1869, doi:10.1128/JVI.02187-07 (2008).
57. Wei, X. et al. Antibody neutralization and escape by HIV-1. Nature 422, 307-312, doi:10.1038/nature01470 (2003).
58. Chen, L. et al. Structural basis of immune evasion at the site of CD4 attachment on HIV-1 gp120. Science 326, 1123-1127, doi:10.1126/science.1175868 (2009).
59. Kwong, P. D. et al. Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody. Nature 393, 648-659 (1998).
60. Spearman, P. et al. A trimeric, V2-deleted HIV-1 envelope glycoprotein vaccine elicits potent neutralizing antibodies but limited breadth of neutralization in human volunteers. J Infect Dis 203, 1165-1173, doi:10.1093/infdis/jiq175 (2011).
61. Cox, J. H. et al. Inclusion of a CRF01-AEHIV envelope protein boost with a DNA/ MVA prime-boost vaccine: Impact on humoral and cellular immunogenicity and viral load reduction after SHIV-E challenge. Vaccine 30, 1830-1840, doi:10.1016/ j.vaccine.2011.12.131 (2012).
62. Kwon, Y. D. 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 U S A 109, 5663-5668, doi:10.1073/pnas.1112391109 (2012).
63. Stricher, F. et al. Combinatorial optimization of a CD4-mimetic miniprotein and cocrystal structures with HIV-1 gp120 envelope glycoprotein. J Mol Biol 382, 510-524, doi:10.1016/j.jmb.2008.06.069 (2008).
64. Ludtke, S. J., Baldwin, P. R. & Chiu, W. EMAN: semiautomated software for highresolution single-particle reconstructions. J Struct Biol 128, 82-97, doi:10.1006/ jsbi.1999.4174 (1999).
65. Pettersen, E. F. et al. UCSF Chimera-a visualization system for exploratory research and analysis. J Comput Chem 25, 1605-1612, doi:10.1002/jcc.20084 (2004).
66. Wriggers, W. Using Situs for the integration of multi-resolution structures. Biophys Rev 2, 21-27, doi:10.1007/s12551-009-0026-3 (2010).