Antigenic Properties of the Human Immunodeficiency Virus Envelope Glycoprotein Gp120 on Virions Bound to Target Cells

1. Berger E.A., Murphy P.M., and Farber J.M., Chemokine receptors as HIV-1 coreceptors: roles in viral entry, tropism, and disease. Annu Rev Immunol, 1999. 17: p. 657–700. 10358771

2. Frank I. and Pope M., The enigma of dendritic cell-immunodeficiency virus interplay. Curr Mol Med, 2002. 2(3): p. 229–48. 12041727

3. Teleshova N., Frank I., and Pope M., Immunodeficiency virus exploitation of dendritic cells in the early steps of infection. J Leukoc Biol, 2003. 74(5): p. 683–90. 12960236

4. Melikyan G.B., Membrane fusion mediated by human immunodeficiency virus envelope glycoprotein. Curr Top Membr, 2011. 68: p. 81–106. doi: 10.1016/B978-0-12-385891-7.00004-0 21771496

5. Eckert D.M. and Kim P.S., Mechanisms of viral membrane fusion and its inhibition. Annu Rev Biochem, 2001. 70: p. 777–810. 11395423

6. Doms R.W. and Trono D., The plasma membrane as a combat zone in the HIV battlefield. Genes Dev, 2000. 14(21): p. 2677–88. 11069884

7. Feng Y., et al., HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science, 1996. 272(5263): p. 872–7. 8629022

8. Alkhatib G., et al., CC CKR5: a RANTES, MIP-1alpha, MIP-1beta receptor as a fusion cofactor for macrophage-tropic HIV-1. Science, 1996. 272(5270): p. 1955–8. 8658171

9. Choe H., et al., The beta-chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates. Cell, 1996. 85(7): p. 1135–48. 8674119

10. Deng H., et al., Identification of a major co-receptor for primary isolates of HIV-1. Nature, 1996. 381(6584): p. 661–6. 8649511

11. Dragic T., et al., HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5. Nature, 1996. 381(6584): p. 667–73. 8649512

12. Wu L., et al., CD4-induced interaction of primary HIV-1 gp120 glycoproteins with the chemokine receptor CCR-5. Nature, 1996. 384(6605): p. 179–83. 8906795

13. Melikyan G.B., HIV entry: a game of hide-and-fuse? Curr Opin Virol, 2014. 4: p. 1–7. doi: 10.1016/j.coviro.2013.09.004 24525288

14. Miyauchi K., et al., HIV enters cells via endocytosis and dynamin-dependent fusion with endosomes. Cell, 2009. 137(3): p. 433–44. doi: 10.1016/j.cell.2009.02.046 19410541

15. Platt E.J., Gomes M.M., and Kabat D., Reversible and Efficient Activation of HIV-1 Cell Entry by a Tyrosine Sulfated Peptide Dissects Endocytic Entry and Inhibitor Mechanisms. J Virol, 2014.

16. Finnegan C.M., et al., Antigenic properties of the human immunodeficiency virus envelope during cell-cell fusion. J Virol, 2001. 75(22): p. 11096–105. 11602749

17. Finnegan C.M., et al., Antigenic properties of the human immunodeficiency virus transmembrane glycoprotein during cell-cell fusion. J Virol, 2002. 76(23): p. 12123–34. 12414953

18. Devico A., et al., Covalently crosslinked complexes of human immunodeficiency virus type 1 (HIV-1) gp120 and CD4 receptor elicit a neutralizing immune response that includes antibodies selective for primary virus isolates. Virology, 1996. 218(1): p. 258–63. 8615032

19. DeVico A.L., et al., Monoclonal antibodies raised against covalently crosslinked complexes of human immunodeficiency virus type 1 gp120 and CD4 receptor identify a novel complex-dependent epitope on gp 120. Virology, 1995. 211(2): p. 583–8. 7544051

20. LaCasse R.A., et al., Fusion-competent vaccines: broad neutralization of primary isolates of HIV. Science, 1999. 283(5400): p. 357–62. 9888845

21. Salzwedel K., et al., Sequential CD4-coreceptor interactions in human immunodeficiency virus type 1 Env function: soluble CD4 activates Env for coreceptor-dependent fusion and reveals blocking activities of antibodies against cryptic conserved epitopes on gp120. J Virol, 2000. 74(1): p. 326–33. 10590121

22. Liu J., et al., Molecular architecture of native HIV-1 gp120 trimers. Nature, 2008. 455(7209): p. 109–13. doi: 10.1038/nature07159 18668044

23. Burton D.R., et al., Efficient neutralization of primary isolates of HIV-1 by a recombinant human monoclonal antibody. Science, 1994. 266(5187): p. 1024–7. 7973652

24. Poignard P., et al., 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, 2003. 77(1): p. 353–65. 12477840

25. Zhou T., et al., Multidonor analysis reveals structural elements, genetic determinants, and maturation pathway for HIV-1 neutralization by VRC01-class antibodies. Immunity, 2013. 39(2): p. 245–58. doi: 10.1016/j.immuni.2013.04.012 23911655

26. Zhou T., et al., Structural basis for broad and potent neutralization of HIV-1 by antibody VRC01. Science, 2010. 329(5993): p. 811–7. doi: 10.1126/science.1192819 20616231

27. Scharf L., et al., Antibody 8ANC195 reveals a site of broad vulnerability on the HIV-1 envelope spike. Cell Rep, 2014. 7(3): p. 785–95. doi: 10.1016/j.celrep.2014.04.001 24767986

28. Klein F., et al., 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, 2012. 209(8): p. 1469–79. doi: 10.1084/jem.20120423 22826297

29. West A.P. Jr., et al., Structural basis for germ-line gene usage of a potent class of antibodies targeting the CD4-binding site of HIV-1 gp120. Proc Natl Acad Sci U S A, 2012. 109(30): p. E2083–90. doi: 10.1073/pnas.1208984109 22745174

30. Calarese D.A., et al., Dissection of the carbohydrate specificity of the broadly neutralizing anti-HIV-1 antibody 2G12. Proc Natl Acad Sci U S A, 2005. 102(38): p. 13372–7. 16174734

31. Walker L.M., et al., Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target. Science, 2009. 326(5950): p. 285–9. doi: 10.1126/science.1178746 19729618

32. McLellan J.S., et al., Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9. Nature, 2011. 480(7377): p. 336–43. doi: 10.1038/nature10696 22113616

33. Julien J.P., et al., Asymmetric recognition of the HIV-1 trimer by broadly neutralizing antibody PG9. Proc Natl Acad Sci U S A, 2013. 110(11): p. 4351–6. doi: 10.1073/pnas.1217537110 23426631

34. Doores K.J. and Burton D.R., Variable loop glycan dependency of the broad and potent HIV-1-neutralizing antibodies PG9 and PG16. J Virol, 2010. 84(20): p. 10510–21. doi: 10.1128/JVI.00552-10 20686044

35. Walker L.M., et al., Broad neutralization coverage of HIV by multiple highly potent antibodies. Nature, 2011. 477(7365): p. 466–70. doi: 10.1038/nature10373 21849977

36. Kong L., et al., Supersite of immune vulnerability on the glycosylated face of HIV-1 envelope glycoprotein gp120. Nat Struct Mol Biol, 2013. 20(7): p. 796–803. doi: 10.1038/nsmb.2594 23708606

37. Pejchal R., et al., A potent and broad neutralizing antibody recognizes and penetrates the HIV glycan shield. Science, 2011. 334(6059): p. 1097–103. doi: 10.1126/science.1213256 21998254

38. Moldt B., et al., 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, 2012. 109(46): p. 18921–5. doi: 10.1073/pnas.1214785109 23100539

39. Pejchal R., et al., Structure and function of broadly reactive antibody PG16 reveal an H3 subdomain that mediates potent neutralization of HIV-1. Proc Natl Acad Sci U S A, 2010. 107(25): p. 11483–8. doi: 10.1073/pnas.1004600107 20534513

40. Ferrari G., 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(14): p. 7029–36. doi: 10.1128/JVI.00171-11 21543485

41. Cavacini L.A., et al., Functional and molecular characterization of human monoclonal antibody reactive with the immunodominant region of HIV type 1 glycoprotein 41. AIDS Res Hum Retroviruses, 1998. 14(14): p. 1271–80. 9764911

42. Melikyan G.B., et al., Evidence that the transition of HIV-1 gp41 into a six-helix bundle, not the bundle configuration, induces membrane fusion. J Cell Biol, 2000. 151(2): p. 413–23. 11038187

43. Labrijn A.F., et al., Access of antibody molecules to the conserved coreceptor binding site on glycoprotein gp120 is sterically restricted on primary human immunodeficiency virus type 1. J Virol, 2003. 77(19): p. 10557–65. 12970440

44. Crooks E.T., et al., Enzyme digests eliminate nonfunctional Env from HIV-1 particle surfaces, leaving native Env trimers intact and viral infectivity unaffected. J Virol, 2011. 85(12): p. 5825–39. doi: 10.1128/JVI.00154-11 21471242

45. Scherer E.M., et al., Aromatic residues at the edge of the antibody combining site facilitate viral glycoprotein recognition through membrane interactions. Proc Natl Acad Sci U S A, 2010. 107(4): p. 1529–34. doi: 10.1073/pnas.0909680107 20080706

46. Stiegler G., et al., A potent cross-clade neutralizing human monoclonal antibody against a novel epitope on gp41 of human immunodeficiency virus type 1. AIDS Res Hum Retroviruses, 2001. 17(18): p. 1757–65. 11788027

47. Binley J.M., et al., Comprehensive cross-clade neutralization analysis of a panel of anti-human immunodeficiency virus type 1 monoclonal antibodies. J Virol, 2004. 78(23): p. 13232–52. 15542675

48. Cavacini L. and Posner M., Native HIV type 1 virion surface structures: relationships between antibody binding and neutralization or lessons from the viral capture assay. AIDS Res Hum Retroviruses, 2004. 20(4): p. 435–41. 15157362

49. Peachman K.K., et al., The effect of sCD4 on the binding and accessibility of HIV-1 gp41 MPER epitopes to human monoclonal antibodies. Virology, 2010. 408(2): p. 213–23. doi: 10.1016/j.virol.2010.09.029 20961591

50. de Rosny E., et al., Binding of the 2F5 monoclonal antibody to native and fusion-intermediate forms of human immunodeficiency virus type 1 gp41: implications for fusion-inducing conformational changes. J Virol, 2004. 78(5): p. 2627–31. 14963170

51. Ray K., et al., Antigenic properties of the HIV envelope on virions in solution. J Virol, 2014. 88(3): p. 1795–808. doi: 10.1128/JVI.03048-13 24284318

52. DeVico A.L., CD4-induced epitopes in the HIV envelope glycoprotein, gp120. Curr HIV Res, 2007. 5(6): p. 561–71. 18045112

53. Baum L.L., et al., HIV-1 gp120-specific antibody-dependent cell-mediated cytotoxicity correlates with rate of disease progression. J Immunol, 1996. 157(5): p. 2168–73. 8757343

54. Forthal D.N., et al., Antibody-dependent cellular cytotoxicity independently predicts survival in severely immunocompromised human immunodeficiency virus-infected patients. J Infect Dis, 1999. 180(4): p. 1338–41. 10479168

55. Guan Y., et al., 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, 2013. 110(1): p. E69–78. doi: 10.1073/pnas.1217609110 23237851

56. Forthal D.N. and Landucci G., In vitro reduction of virus infectivity by antibody-dependent cell-mediated immunity. J Immunol Methods, 1998. 220(1–2): p. 129–38. 9839938

57. Kramski M., et al., Anti-HIV-1 antibody-dependent cellular cytotoxicity mediated by hyperimmune bovine colostrum IgG. Eur J Immunol, 2012. 42(10): p. 2771–81. doi: 10.1002/eji.201242469 22730083

58. Kramski M., et al., Role of monocytes in mediating HIV-specific antibody-dependent cellular cytotoxicity. J Immunol Methods, 2012. 384(1–2): p. 51–61. doi: 10.1016/j.jim.2012.07.006 22841577

59. Kramski M., et al., HIV-specific antibody immunity mediated through NK cells and monocytes. Curr HIV Res, 2013. 11(5): p. 388–406. 24191935

60. Moore J.P. and Sodroski J., Antibody cross-competition analysis of the human immunodeficiency virus type 1 gp120 exterior envelope glycoprotein. J Virol, 1996. 70(3): p. 1863–72. 8627711

61. 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, 1997. 71(12): p. 9722–31. 9371638

62. Wyatt R., et al., The antigenic structure of the HIV gp120 envelope glycoprotein. Nature, 1998. 393(6686): p. 705–11. 9641684

63. Burrer R., et al., 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, 2005. 333(1): p. 102–13. 15708596

64. Nyambi P.N., et al., Mapping of epitopes exposed on intact human immunodeficiency virus type 1 (HIV-1) virions: a new strategy for studying the immunologic relatedness of HIV-1. J Virol, 1998. 72(11): p. 9384–91. 9765494

65. Leaman D.P., Kinkead H., and Zwick M.B., In-solution virus capture assay helps deconstruct heterogeneous antibody recognition of human immunodeficiency virus type 1. Journal of Virology, 2010. 84(7): p. 3382–95. doi: 10.1128/JVI.02363-09 20089658

66. Liu P., et al., Infectious virion capture by HIV-1 gp120-specific IgG from RV144 vaccinees. J Virol, 2013. 87(14): p. 7828–36. doi: 10.1128/JVI.02737-12 23658446

67. Dennison S.M., et al., Vaccine induced HIV-1 envelope gp120 Constant Region 1-specific Antibodies Expose a CD4-inducible Epitope and Block the Interaction of HIV-1 gp140 With Galactosylceramide. J Virol, 2014.

68. Sun Y., et al., Antibody-dependent cell-mediated cytotoxicity in simian immunodeficiency virus-infected rhesus monkeys. J Virol, 2011. 85(14): p. 6906–12. doi: 10.1128/JVI.00326-11 21593181

69. Alpert M.D., et al., ADCC develops over time during persistent infection with live-attenuated SIV and is associated with complete protection against SIV(mac)251 challenge. PLoS Pathog, 2012. 8(8): p. e1002890. doi: 10.1371/journal.ppat.1002890 22927823

70. Banks N.D., et al., Sustained antibody-dependent cell-mediated cytotoxicity (ADCC) in SIV-infected macaques correlates with delayed progression to AIDS. AIDS Res Hum Retroviruses, 2002. 18(16): p. 1197–205. 12487826

71. Barouch D.H., et al., Vaccine protection against acquisition of neutralization-resistant SIV challenges in rhesus monkeys. Nature, 2012. 482(7383): p. 89–93. doi: 10.1038/nature10766 22217938

72. Florese R.H., et al., Contribution of nonneutralizing vaccine-elicited antibody activities to improved protective efficacy in rhesus macaques immunized with Tat/Env compared with multigenic vaccines. J Immunol, 2009. 182(6): p. 3718–27. doi: 10.4049/jimmunol.0803115 19265150

73. Gomez-Roman V.R., et al., An adenovirus-based HIV subtype B prime/boost vaccine regimen elicits antibodies mediating broad antibody-dependent cellular cytotoxicity against non-subtype B HIV strains. J Acquir Immune Defic Syndr, 2006. 43(3): p. 270–7. 16940858

74. Hessell A.J., et al., Fc receptor but not complement binding is important in antibody protection against HIV. Nature, 2007. 449(7158): p. 101–4. 17805298

75. Hidajat R., et al., Correlation of vaccine-elicited systemic and mucosal nonneutralizing antibody activities with reduced acute viremia following intrarectal simian immunodeficiency virus SIVmac251 challenge of rhesus macaques. J Virol, 2009. 83(2): p. 791–801. doi: 10.1128/JVI.01672-08 18971271

76. Xiao P., et al., Multiple vaccine-elicited nonneutralizing antienvelope antibody activities contribute to protective efficacy by reducing both acute and chronic viremia following simian/human immunodeficiency virus SHIV89.6P challenge in rhesus macaques. J Virol, 2010. 84(14): p. 7161–73. doi: 10.1128/JVI.00410-10 20444898

77. Gomez-Roman V.R., et al., Vaccine-elicited antibodies mediate antibody-dependent cellular cytotoxicity correlated with significantly reduced acute viremia in rhesus macaques challenged with SIVmac251. J Immunol, 2005. 174(4): p. 2185–9. 15699150

78. Haynes B.F., et al., Immune-correlates analysis of an HIV-1 vaccine efficacy trial. N Engl J Med, 2012. 366(14): p. 1275–86. doi: 10.1056/NEJMoa1113425 22475592

79. Mabuka J., et al., HIV-specific antibodies capable of ADCC are common in breastmilk and are associated with reduced risk of transmission in women with high viral loads. PLoS Pathog, 2012. 8(6): p. e1002739. doi: 10.1371/journal.ppat.1002739 22719248

80. Forthal D.N., et al., FcgammaRIIa genotype predicts progression of HIV infection. J Immunol, 2007. 179(11): p. 7916–23. 18025239

81. Ljunggren K., et al., 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(2): p. 198–202. 2299204

82. Burton D.R., et al., HIV vaccine design and the neutralizing antibody problem. Nat Immunol, 2004. 5(3): p. 233–6. 14985706

83. Poignard P., et al., Gp120: biologic aspects of structural features. Annu Rev Immunol, 2001. 19: p. 253–74. 11244037

84. Burton D.R., Stanfield R.L., and Wilson I.A., Antibody vs. HIV in a clash of evolutionary titans. Proc Natl Acad Sci U S A, 2005. 102(42): p. 14943–8. 16219699

85. Finzi A., et al., Topological layers in the HIV-1 gp120 inner domain regulate gp41 interaction and CD4-triggered conformational transitions. Mol Cell, 2010. 37(5): p. 656–67. doi: 10.1016/j.molcel.2010.02.012 20227370

86. Moore J.P., et al., 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(12): p. 8350–64. 7525988

87. Pancera M., et al., Structure of HIV-1 gp120 with gp41-interactive region reveals layered envelope architecture and basis of conformational mobility. Proc Natl Acad Sci U S A, 2010. 107(3): p. 1166–71. doi: 10.1073/pnas.0911004107 20080564

88. Thali M., et al., Characterization of conserved human immunodeficiency virus type 1 gp120 neutralization epitopes exposed upon gp120-CD4 binding. J Virol, 1993. 67(7): p. 3978–88. 7685405

89. Moore J.P., et al., 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(11): p. 6836–47. 7933065

90. Xiang S.H., et al., Characterization of CD4-induced epitopes on the HIV type 1 gp120 envelope glycoprotein recognized by neutralizing human monoclonal antibodies. AIDS Res Hum Retroviruses, 2002. 18(16): p. 1207–17. 12487827

91. Saphire E.O., et al., Crystal structure of a neutralizing human IGG against HIV-1: a template for vaccine design. Science, 2001. 293(5532): p. 1155–9. 11498595

92. Burton D.R., et al., A large array of human monoclonal antibodies to type 1 human immunodeficiency virus from combinatorial libraries of asymptomatic seropositive individuals. Proc Natl Acad Sci U S A, 1991. 88(22): p. 10134–7. 1719545

93. Roben P., et al., Recognition properties of a panel of human recombinant Fab fragments to the CD4 binding site of gp120 that show differing abilities to neutralize human immunodeficiency virus type 1. J Virol, 1994. 68(8): p. 4821–8. 7518527

94. Trkola A., et al., Human monoclonal antibody 2G12 defines a distinctive neutralization epitope on the gp120 glycoprotein of human immunodeficiency virus type 1. J Virol, 1996. 70(2): p. 1100–8. 8551569

95. Sanders R.W., et al., The mannose-dependent epitope for neutralizing antibody 2G12 on human immunodeficiency virus type 1 glycoprotein gp120. J Virol, 2002. 76(14): p. 7293–305. 12072528

96. Scanlan C.N., et al., The broadly neutralizing anti-human immunodeficiency virus type 1 antibody 2G12 recognizes a cluster of alpha1—>2 mannose residues on the outer face of gp120. J Virol, 2002. 76(14): p. 7306–21. 12072529

97. Murin C.D., et al., Structure of 2G12 Fab2 in Complex with Soluble and Fully Glycosylated HIV-1 Env by Negative-Stain Single Particle Electron Microscopy. J Virol, 2014.

98. Derdeyn C.A., et al., Sensitivity of human immunodeficiency virus type 1 to the fusion inhibitor T-20 is modulated by coreceptor specificity defined by the V3 loop of gp120. Journal of virology, 2000. 74(18): p. 8358–67. 10954535

99. Platt E.J., et al., Evidence that ecotropic murine leukemia virus contamination in TZM-bl cells does not affect the outcome of neutralizing antibody assays with human immunodeficiency virus type 1. Journal of virology, 2009. 83(16): p. 8289–92. doi: 10.1128/JVI.00709-09 19474095

100. Platt E.J., et al., Effects of CCR5 and CD4 cell surface concentrations on infections by macrophagetropic isolates of human immunodeficiency virus type 1. Journal of virology, 1998. 72(4): p. 2855–64. 9525605

101. Takeuchi Y., McClure M.O., and Pizzato M., Identification of gammaretroviruses constitutively released from cell lines used for human immunodeficiency virus research. Journal of virology, 2008. 82(24): p. 12585–8. doi: 10.1128/JVI.01726-08 18842727

102. Frey S., et al., Temperature dependence of cell-cell fusion induced by the envelope glycoprotein of human immunodeficiency virus type 1. J Virol, 1995. 69(3): p. 1462–72. 7853478

103. Mkrtchyan S.R., et al., Ternary complex formation of human immunodeficiency virus type 1 Env, CD4, and chemokine receptor captured as an intermediate of membrane fusion. J Virol, 2005. 79(17): p. 11161–9. 16103167

104. Eckhardt M., et al., A SNAP-tagged derivative of HIV-1—a versatile tool to study virus-cell interactions. PLoS One, 2011. 6(7): p. e22007. doi: 10.1371/journal.pone.0022007 21799764

105. Dale B.M., et al., Cell-to-cell transfer of HIV-1 via virological synapses leads to endosomal virion maturation that activates viral membrane fusion. Cell Host Microbe, 2011. 10(6): p. 551–62. doi: 10.1016/j.chom.2011.10.015 22177560

106. Lehmann M., et al., Quantitative multicolor super-resolution microscopy reveals tetherin HIV-1 interaction. PLoS Pathog, 2011. 7(12): p. e1002456. doi: 10.1371/journal.ppat.1002456 22194693

107. Pereira C.F., et al., HIV taken by STORM: super-resolution fluorescence microscopy of a viral infection. Virol J, 2012. 9: p. 84. doi: 10.1186/1743-422X-9-84 22551453

108. Roy N.H., et al., Clustering and mobility of HIV-1 Env at viral assembly sites predict its propensity to induce cell-cell fusion. J Virol, 2013. 87(13): p. 7516–25. doi: 10.1128/JVI.00790-13 23637402

109. Van Engelenburg S.B., et al., Distribution of ESCRT machinery at HIV assembly sites reveals virus scaffolding of ESCRT subunits. Science, 2014. 343(6171): p. 653–6. doi: 10.1126/science.1247786 24436186

110. Chojnacki J., et al., Maturation-dependent HIV-1 surface protein redistribution revealed by fluorescence nanoscopy. Science, 2012. 338(6106): p. 524–8. doi: 10.1126/science.1226359 23112332

111. Muranyi W., et al., Super-resolution microscopy reveals specific recruitment of HIV-1 envelope proteins to viral assembly sites dependent on the envelope C-terminal tail. PLoS Pathog, 2013. 9(2): p. e1003198. doi: 10.1371/journal.ppat.1003198 23468635

112. Grove J., Super-resolution microscopy: a virus' eye view of the cell. Viruses, 2014. 6(3): p. 1365–78. doi: 10.3390/v6031365 24651030

113. Huang B., et al., Three-dimensional super-resolution imaging by stochastic optical reconstruction microscopy. Science, 2008. 319(5864): p. 810–3. doi: 10.1126/science.1153529 18174397

114. Burton D.R. and Montefiori D.C., The antibody response in HIV-1 infection. AIDS, 1997. 11 Suppl A: p. S87–98. 9451972

115. Calarese D.A., et al., Antibody domain exchange is an immunological solution to carbohydrate cluster recognition. Science, 2003. 300(5628): p. 2065–71. 12829775

116. Scanlan C.N., et al., The carbohydrate epitope of the neutralizing anti-HIV-1 antibody 2G12. Adv Exp Med Biol, 2003. 535: p. 205–18. 14714897

117. Dalgleish A.G., et al., The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature, 1984. 312(5996): p. 763–7. 6096719

118. Pal R., et al., Conformational perturbation of the envelope glycoprotein gp120 of human immunodeficiency virus type 1 by soluble CD4 and the lectin succinyl Con A. Virology, 1993. 194(2): p. 833–7. 8503188

119. Sattentau Q.J., et al., Conformational changes induced in the envelope glycoproteins of the human and simian immunodeficiency viruses by soluble receptor binding. J Virol, 1993. 67(12): p. 7383–93. 7693970

120. Sullivan N., et al., CD4-Induced conformational changes in the human immunodeficiency virus type 1 gp120 glycoprotein: consequences for virus entry and neutralization. J Virol, 1998. 72(6): p. 4694–703. 9573233

121. Trkola A., et al., CD4-dependent, antibody-sensitive interactions between HIV-1 and its co-receptor CCR-5. Nature, 1996. 384(6605): p. 184–7. 8906796

122. Wyatt R. and Sodroski J., The HIV-1 envelope glycoproteins: fusogens, antigens, and immunogens. Science, 1998. 280: p. 1884–8. 9632381

123. Nelson J.D., et al., An affinity-enhanced neutralizing antibody against the membrane-proximal external region of human immunodeficiency virus type 1 gp41 recognizes an epitope between those of 2F5 and 4E10. J Virol, 2007. 81(8): p. 4033–43. 17287272

124. Bonsignori 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. Journal of Virology, 2012. 86(21): p. 11521–32. doi: 10.1128/JVI.01023-12 22896626

125. Ferrari G., 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. Journal of virology, 2011. 85(14): p. 7029–36. doi: 10.1128/JVI.00171-11 21543485

126. Veillette M., et al., Interaction with Cellular CD4 Exposes HIV-1 Envelope Epitopes Targeted by Antibody-Dependent Cell-Mediated Cytotoxicity. J Virol, 2014. 88(5): p. 2633–44. doi: 10.1128/JVI.03230-13 24352444

127. Davenport T.M., et al., Isolate-specific differences in the conformational dynamics and antigenicity of HIV-1 gp120. J Virol, 2013. 87(19): p. 10855–73. doi: 10.1128/JVI.01535-13 23903848

128. Kwong P.D., et al., Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody. Nature, 1998. 393: p. 648–59. 9641677

129. Chen B., et al., Structure of an unliganded simian immunodeficiency virus gp120 core. Nature, 2005. 433(7028): p. 834–41. 15729334

130. Kwong P.D., et al., HIV-1 evades antibody-mediated neutralization through conformational masking of receptor-binding sites. Nature, 2002. 420(6916): p. 678–82. 12478295

131. Lyumkis D., et al., Cryo-EM structure of a fully glycosylated soluble cleaved HIV-1 envelope trimer. Science, 2013. 342(6165): p. 1484–90. doi: 10.1126/science.1245627 24179160

132. Sanders R.W., 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(9): p. e1003618. doi: 10.1371/journal.ppat.1003618 24068931

133. Bennett A., et al., Cryoelectron tomographic analysis of an HIV-neutralizing protein and its complex with native viral gp120. J Biol Chem, 2007. 282(38): p. 27754–9. 17599917

134. Sougrat R., et al., Electron tomography of the contact between T cells and SIV/HIV-1: implications for viral entry. PLoS Pathog, 2007. 3(5): p. e63. 17480119

135. Zhu P., et al., Distribution and three-dimensional structure of AIDS virus envelope spikes. Nature, 2006. 441(7095): p. 847–52. 16728975

136. Duncan C.J., et al., High-multiplicity HIV-1 infection and neutralizing antibody evasion mediated by the macrophage-T cell virological synapse. J Virol, 2014. 88(4): p. 2025–34. doi: 10.1128/JVI.03245-13 24307588

137. Platt E.J., Gomes M.M., and Kabat D., Kinetic mechanism for HIV-1 neutralization by antibody 2G12 entails reversible glycan binding that slows cell entry. Proc Natl Acad Sci U S A, 2012. 109(20): p. 7829–34. doi: 10.1073/pnas.1109728109 22547820

138. Briggs J.A., et al., Structural organization of authentic, mature HIV-1 virions and cores. EMBO J, 2003. 22(7): p. 1707–15. 12660176

139. Pang Y., et al., Optical trapping of individual human immunodeficiency viruses in culture fluid reveals heterogeneity with single-molecule resolution. Nat Nanotechnol, 2014.

140. Daecke J., et al., Involvement of clathrin-mediated endocytosis in human immunodeficiency virus type 1 entry. J Virol, 2005. 79(3): p. 1581–94. 15650184

141. de la Vega M., et al., Inhibition of HIV-1 endocytosis allows lipid mixing at the plasma membrane, but not complete fusion. Retrovirology, 2011. 8: p. 99. doi: 10.1186/1742-4690-8-99 22145853

142. Fackler O.T. and Peterlin B.M., Endocytic entry of HIV-1. Curr Biol, 2000. 10(16): p. 1005–8. 10985390

143. Fredericksen B.L., et al., Inhibition of endosomal/lysosomal degradation increases the infectivity of human immunodeficiency virus. J Virol, 2002. 76(22): p. 11440–6. 12388705

144. Marechal V., et al., Cytosolic Gag p24 as an index of productive entry of human immunodeficiency virus type 1. J Virol, 1998. 72(3): p. 2208–12. 9499078

145. von Kleist L., et al., Role of the clathrin terminal domain in regulating coated pit dynamics revealed by small molecule inhibition. Cell, 2011. 146(3): p. 471–84. doi: 10.1016/j.cell.2011.06.025 21816279

146. Vidricaire G., Imbeault M., and Tremblay M.J., Endocytic host cell machinery plays a dominant role in intracellular trafficking of incoming human immunodeficiency virus type 1 in human placental trophoblasts. J Virol, 2004. 78(21): p. 11904–15. 15479831

147. Herold N., et al., HIV-1 entry in SupT1-R5, CEM-ss and primary CD4+ T-cells occurs at the plasma membrane and does not require endocytosis. J Virol, 2014.

148. Iwasaki K. and Omura T., Electron tomography of the supramolecular structure of virus-infected cells. Curr Opin Struct Biol, 2010. 20(5): p. 632–9. doi: 10.1016/j.sbi.2010.08.007 20850967

149. Miyauchi K., Marin M., and Melikyan G.B., Visualization of retrovirus uptake and delivery into acidic endosomes. Biochem J, 2011. 434(3): p. 559–69. doi: 10.1042/BJ20101588 21175427

150. Padilla-Parra S., et al., Fusion of mature HIV-1 particles leads to complete release of a gag-GFP-based content marker and raises the intraviral pH. PLoS One, 2013. 8(8): p. e71002. doi: 10.1371/journal.pone.0071002 23951066

151. Bedinger P., et al., Internalization of the human immunodeficiency virus does not require the cytoplasmic domain of CD4. Nature, 1988. 334(6178): p. 162–5. 3260353

152. Brandt S.M., et al., Association of chemokine-mediated block to HIV entry with coreceptor internalization. J Biol Chem, 2002. 277(19): p. 17291–9. 11782464

153. Maddon P.J., et al., HIV infection does not require endocytosis of its receptor, CD4. Cell, 1988. 54(6): p. 865–74. 3261635

154. McClure M.O., Marsh M., and Weiss R.A., Human immunodeficiency virus infection of CD4-bearing cells occurs by a pH-independent mechanism. EMBO J, 1988. 7(2): p. 513–8. 3259178

155. Stein B.S., et al., pH-independent HIV entry into CD4-positive T cells via virus envelope fusion to the plasma membrane. Cell, 1987. 49(5): p. 659–68. 3107838

156. Pelchen-Matthews A., Clapham P., and Marsh M., Role of CD4 endocytosis in human immunodeficiency virus infection. J Virol, 1995. 69(12): p. 8164–8. 7494343

157. McDonald D., et al., Visualization of the intracellular behavior of HIV in living cells. J Cell Biol, 2002. 159(3): p. 441–52. 12417576

158. Campbell E.M., et al., Labeling HIV-1 virions with two fluorescent proteins allows identification of virions that have productively entered the target cell. Virology, 2007. 360(2): p. 286–93. 17123568

159. Sato A., et al., Targeting of chrolamphenicol acetyltransferase to human immunodeficiency virus particles via Vpr and Vpx. Microbiol Immunol, 1995. 39(12): p. 1015–9. 8789063

160. Wu X., et al., Targeting foreign proteins to human immunodeficiency virus particles via fusion with Vpr and Vpx. J Virol, 1995. 69(6): p. 3389–98. 7745685

161. Liska V., et al., Localization of viral protein X in simian immunodeficiency virus macaque strain and analysis of its packaging requirements. J Gen Virol, 1994. 75 (Pt 11): p. 2955–62. 7964605

162. Wang J.J., Lu Y., and Ratner L., Particle assembly and Vpr expression in human immunodeficiency virus type 1-infected cells demonstrated by immunoelectron microscopy. J Gen Virol, 1994. 75 (Pt 10): p. 2607–14. 7931147

163. Sherman M.P., et al., HIV-1 Vpr displays natural protein-transducing properties: implications for viral pathogenesis. Virology, 2002. 302(1): p. 95–105. 12429519

164. Nikolic D.S., et al., HIV-1 activates Cdc42 and induces membrane extensions in immature dendritic cells to facilitate cell-to-cell virus propagation. Blood, 2011. 118(18): p. 4841–52. doi: 10.1182/blood-2010-09-305417 21562048

165. Steffens C.M. and Hope T.J., Localization of CD4 and CCR5 in living cells. J Virol, 2003. 77(8): p. 4985–91. 12663805

166. Singer II, et al., CCR5, CXCR4, and CD4 are clustered and closely apposed on microvilli of human macrophages and T cells. J Virol, 2001. 75(8): p. 3779–90. 11264367

167. Clavel F. and Charneau P., Fusion from without directed by human immunodeficiency virus particles. J Virol, 1994. 68(2): p. 1179–85. 8289347

168. Bourinbaiar A.S., The ratio of defective HIV-1 particles to replication-competent infectious virions. Acta Virol, 1994. 38(1): p. 59–61. 7520666

169. Kwon Y.J., et al., Determination of infectious retrovirus concentration from colony-forming assay with quantitative analysis. J Virol, 2003. 77(10): p. 5712–20. 12719564

170. Layne S.P., et al., Factors underlying spontaneous inactivation and susceptibility to neutralization of human immunodeficiency virus. Virology, 1992. 189(2): p. 695–714. 1386485

171. Marozsan A.J., et al., Relationships between infectious titer, capsid protein levels, and reverse transcriptase activities of diverse human immunodeficiency virus type 1 isolates. J Virol, 2004. 78(20): p. 11130–41. 15452233

172. Rusert P., et al., Quantification of infectious HIV-1 plasma viral load using a boosted in vitro infection protocol. Virology, 2004. 326(1): p. 113–29. 15262500

173. Platt E.J., et al., Rapid dissociation of HIV-1 from cultured cells severely limits infectivity assays, causes the inactivation ascribed to entry inhibitors, and masks the inherently high level of infectivity of virions. J Virol, 2010. 84(6): p. 3106–10. doi: 10.1128/JVI.01958-09 20042508

174. Fouts T.R., et al., Expression and characterization of a single-chain polypeptide analogue of the human immunodeficiency virus type 1 gp120-CD4 receptor complex. J Virol, 2000. 74(24): p. 11427–36. 11090138

175. Chertova E., et al., Envelope glycoprotein incorporation, not shedding of surface envelope glycoprotein (gp120/SU), Is the primary determinant of SU content of purified human immunodeficiency virus type 1 and simian immunodeficiency virus. J Virol, 2002. 76(11): p. 5315–25. 11991960

176. Zhu P., et al., Electron tomography analysis of envelope glycoprotein trimers on HIV and simian immunodeficiency virus virions. Proc Natl Acad Sci U S A, 2003. 100(26): p. 15812–7. 14668432

177. Bothner B., et al., Evidence of viral capsid dynamics using limited proteolysis and mass spectrometry. J Biol Chem, 1998. 273(2): p. 673–6. 9422714

178. Lewis J.K., et al., Antiviral agent blocks breathing of the common cold virus. Proc Natl Acad Sci U S A, 1998. 95(12): p. 6774–8. 9618488

179. Lin J., et al., Structure of the fab-labeled "breathing" state of native poliovirus. J Virol, 2012. 86(10): p. 5959–62. doi: 10.1128/JVI.05990-11 22398295

180. Hansman G.S., et al., Structural basis for broad detection of genogroup II noroviruses by a monoclonal antibody that binds to a site occluded in the viral particle. J Virol, 2012. 86(7): p. 3635–46. doi: 10.1128/JVI.06868-11 22278249

181. Lok S.M., et al., Binding of a neutralizing antibody to dengue virus alters the arrangement of surface glycoproteins. Nat Struct Mol Biol, 2008. 15(3): p. 312–7. doi: 10.1038/nsmb.1382 18264114

182. Cockburn J.J., et al., Mechanism of dengue virus broad cross-neutralization by a monoclonal antibody. Structure, 2012. 20(2): p. 303–14. doi: 10.1016/j.str.2012.01.001 22285214

183. Dowd K.A., et al., A dynamic landscape for antibody binding modulates antibody-mediated neutralization of West Nile virus. PLoS Pathog, 2011. 7(6): p. e1002111. doi: 10.1371/journal.ppat.1002111 21738473

184. Kuhmann S.E., et al., Polymorphisms in the CCR5 genes of African green monkeys and mice implicate specific amino acids in infections by simian and human immunodeficiency viruses. J Virol, 1997. 71(11): p. 8642–56. 9343222

185. Kimpton J. and Emerman M., Detection of replication-competent and pseudotyped human immunodeficiency virus with a sensitive cell line on the basis of activation of an integrated beta-galactosidase gene. Journal of virology, 1992. 66(4): p. 2232–9. 1548759

186. Schaeffer E., Geleziunas R., and Greene W.C., Human immunodeficiency virus type 1 Nef functions at the level of virus entry by enhancing cytoplasmic delivery of virions. Journal of virology, 2001. 75(6): p. 2993–3000. 11222724

187. Wei X., et al., Emergence of resistant human immunodeficiency virus type 1 in patients receiving fusion inhibitor (T-20) monotherapy. Antimicrobial agents and chemotherapy, 2002. 46(6): p. 1896–905. 12019106

188. Wei X., et al., Antibody neutralization and escape by HIV-1. Nature, 2003. 422(6929): p. 307–12. 12646921

189. Binley J.M., et al., Redox-triggered infection by disulfide-shackled human immunodeficiency virus type 1 pseudovirions. Journal of virology, 2003. 77(10): p. 5678–84. 12719560

190. Tardif M.R. and Tremblay M.J., Presence of host ICAM-1 in human immunodeficiency virus type 1 virions increases productive infection of CD4+ T lymphocytes by favoring cytosolic delivery of viral material. J Virol, 2003. 77(22): p. 12299–309. 14581566

191. Kondo N. and Melikyan G.B., Intercellular adhesion molecule 1 promotes HIV-1 attachment but not fusion to target cells. PLoS One, 2012. 7(9): p. e44827. doi: 10.1371/journal.pone.0044827 22970312

192. Li M., et al., Genetic and neutralization properties of subtype C human immunodeficiency virus type 1 molecular env clones from acute and early heterosexually acquired infections in Southern Africa. Journal of virology, 2006. 80(23): p. 11776–90. 16971434

193. Hess S.T., et al., Biological and chemical applications of fluorescence correlation spectroscopy: a review. Biochemistry, 2002. 41(3): p. 697–705. 11790090

194. Anderson K., et al., A new configuration of the Zeiss LSM 510 for simulltaneous optical separation of green and red fluorescent protein pairs. Cytometry, 2006. 69: p. 920–929. 16969813