Different Infectivity of HIV-1 Strains Is Linked to Number of Envelope Trimers Required for Entry

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Our estimates of the HIV-1 entry stoichiometry, that is the number of envelope glycoprotein trimers needed to mediate fusion of viral and target cell membrane, close an important gap in our understanding of the HIV entry process. As we show, stoichiometric requirements for envelope trimers differ between HIV strains and steer virus entry efficacy and virus entry kinetics. Thus, the entry stoichiometry has important implications for HIV transmission, as demands on trimer numbers will dictate the infectivity of virus populations, target cell preferences and virus inactivation by trimer-targeting inhibitors and neutralizing antibodies. Beyond this, our data contribute to the general understanding of mechanisms and energetic requirements of protein-mediated membrane fusion, as HIV entry proved to follow similar stoichiometries as described for Influenza virus HA and SNARE protein mediated membrane fusion. In summary, our findings provide a relevant contribution towards a refined understanding of HIV-1 entry and pathogenesis with particular importance for ongoing efforts to generate neutralizing antibody based therapeutics and vaccines targeting the HIV-1 envelope trimer.

Vyšlo v časopise: Different Infectivity of HIV-1 Strains Is Linked to Number of Envelope Trimers Required for Entry. PLoS Pathog 11(1): e32767. doi:10.1371/journal.ppat.1004595
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004595

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Zdroje

1. KlassePJ (2012) The molecular basis of HIV entry. Cell Microbiol 14 : 1183–1192.

2. WilenCB, TiltonJC, DomsRW (2012) Molecular mechanisms of HIV entry. Adv Exp Med Biol 726 : 223–242.

3. MascolaJR, HaynesBF (2013) HIV-1 neutralizing antibodies: understanding nature's pathways. Immunol Rev 254 : 225–244.

4. KleinF, MouquetH, DosenovicP, ScheidJF, ScharfL, et al. (2013) Antibodies in HIV-1 vaccine development and therapy. Science 341 : 1199–1204.

5. PanceraM, ZhouT, DruzA, GeorgievIS, SotoC, et al. (2014) Structure and immune recognition of trimeric pre-fusion HIV-1 Env. Nature. 2014 514(7523): 455–61.

6. PollakisG, PaxtonWA (2012) Use of (alternative) coreceptors for HIV entry. Curr Opin HIV AIDS 7 : 440–449.

7. BlumenthalR, DurellS, ViardM (2012) HIV entry and envelope glycoprotein-mediated fusion. J Biol Chem 287 : 40841–40849.

8. HarrisonSC (2008) Viral membrane fusion. Nat Struct Mol Biol 15 : 690–698.

9. CohenFS, MelikyanGB (2004) The energetics of membrane fusion from binding, through hemifusion, pore formation, and pore enlargement. J Membr Biol 199 : 1–14.

10. MelikyanGB (2008) Common principles and intermediates of viral protein-mediated fusion: the HIV-1 paradigm. Retrovirology 5 : 111.

11. JahnR, LangT, SudhofTC (2003) Membrane fusion. Cell 112 : 519–533.

12. GalloSA, ReevesJD, GargH, FoleyB, DomsRW, et al. (2006) Kinetic studies of HIV-1 and HIV-2 envelope glycoprotein-mediated fusion. Retrovirology 3 : 90.

13. YangX, KurtevaS, RenX, LeeS, SodroskiJ (2005) Stoichiometry of envelope glycoprotein trimers in the entry of human immunodeficiency virus type 1. J Virol 79 : 12132–12147.

14. KlassePJ (2007) Modeling how many envelope glycoprotein trimers per virion participate in human immunodeficiency virus infectivity and its neutralization by antibody. Virology 369 : 245–262.

15. MagnusC, RusertP, BonhoefferS, TrkolaA, RegoesRR (2009) Estimating the stoichiometry of human immunodeficiency virus entry. J Virol 83 : 1523–1531.

16. FloydDL, RagainsJR, SkehelJJ, HarrisonSC, van OijenAM (2008) Single-particle kinetics of influenza virus membrane fusion. Proc Natl Acad Sci U S A 105 : 15382–15387.

17. IvanovicT, ChoiJL, WhelanSP, van OijenAM, HarrisonSC (2013) Influenza-virus membrane fusion by cooperative fold-back of stochastically induced hemagglutinin intermediates. Elife 2: e00333.

18. DanieliT, PelletierSL, HenisYI, WhiteJM (1996) Membrane fusion mediated by the influenza virus hemagglutinin requires the concerted action of at least three hemagglutinin trimers. J Cell Biol 133 : 559–569.

19. SougratR, BartesaghiA, LifsonJD, BennettAE, BessJW, et al. (2007) Electron tomography of the contact between T cells and SIV/HIV-1: implications for viral entry. PLoS Pathog 3: e63.

20. KuhmannSE, PlattEJ, KozakSL, KabatD (2000) Cooperation of multiple CCR5 coreceptors is required for infections by human immunodeficiency virus type 1. J Virol 74 : 7005–7015.

21. PlattEJ, DurninJP, ShindeU, KabatD (2007) An allosteric rheostat in HIV-1 gp120 reduces CCR5 stoichiometry required for membrane fusion and overcomes diverse entry limitations. J Mol Biol 374 : 64–79.

22. BurtonDR, PoignardP, StanfieldRL, WilsonIA (2012) Broadly neutralizing antibodies present new prospects to counter highly antigenically diverse viruses. Science 337 : 183–186.

23. ChertovaE, Bess JrJWJr, CriseBJ, SowderIR, SchadenTM, et al. (2002) 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 76 : 5315–5325.

24. LayneSP, MergesMJ, DemboM, SpougeJL, ConleySR, et al. (1992) Factors underlying spontaneous inactivation and susceptibility to neutralization of human immunodeficiency virus. Virology 189 : 695–714.

25. ZhuP, ChertovaE, BessJJr, LifsonJD, ArthurLO, et al. (2003) Electron tomography analysis of envelope glycoprotein trimers on HIV and simian immunodeficiency virus virions. Proc Natl Acad Sci U S A 100 : 15812–15817.

26. ZhuP, LiuJ, BessJJr, ChertovaE, LifsonJD, et al. (2006) Distribution and three-dimensional structure of AIDS virus envelope spikes. Nature 441 : 847–852.

27. LiuJ, BartesaghiA, BorgniaMJ, SapiroG, SubramaniamS (2008) Molecular architecture of native HIV-1 gp120 trimers. Nature 455 : 109–113.

28. ChojnackiJ, StaudtT, GlassB, BingenP, EngelhardtJ, et al. (2012) Maturation-dependent HIV-1 surface protein redistribution revealed by fluorescence nanoscopy. Science 338 : 524–528.

29. LouderMK, SamborA, ChertovaE, HunteT, BarrettS, et al. (2005) HIV-1 envelope pseudotyped viral vectors and infectious molecular clones expressing the same envelope glycoprotein have a similar neutralization phenotype, but culture in peripheral blood mononuclear cells is associated with decreased neutralization sensitivity. Virology 339 : 226–238.

30. FreedEO, MyersDJ, RisserR (1989) Mutational analysis of the cleavage sequence of the human immunodeficiency virus type 1 envelope glycoprotein precursor gp160. J Virol 63 : 4670–4675.

31. GuoHG, VeroneseFM, TschachlerE, PalR, KalyanaramanVS, et al. (1990) Characterization of an HIV-1 point mutant blocked in envelope glycoprotein cleavage. Virology 174 : 217–224.

32. FreedEO, DelwartEL, BuchschacherGLJr, PanganibanAT (1992) A mutation in the human immunodeficiency virus type 1 transmembrane glycoprotein gp41 dominantly interferes with fusion and infectivity. Proc Natl Acad Sci U S A 89 : 70–74.

33. CarlsonLA, BriggsJA, GlassB, RichesJD, SimonMN, et al. (2008) Three-dimensional analysis of budding sites and released virus suggests a revised model for HIV-1 morphogenesis. Cell Host Microbe 4 : 592–599.

34. CaoJ, SullivanN, DesjardinE, ParolinC, RobinsonJ, et al. (1997) 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.

35. WyattR, SullivanN, ThaliM, RepkeH, HoD, et al. (1993) Functional and immunologic characterization of human immunodeficiency virus type 1 envelope glycoproteins containing deletions of the major variable regions. J Virol 67 : 4557–4565.

36. StamatatosL, WiskerchenM, Cheng-MayerC (1998) 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 Res Hum Retroviruses 14 : 1129–1139.

37. PalmerC, BalfeP, FoxD, MayJC, FrederikssonR, et al. (1996) Functional characterization of the V1V2 region of human immunodeficiency virus type 1. Virology. United States pp 436–449.

38. BrandenbergOF, RusertP, MagnusC, WeberJ, BoniJ, et al. (2014) Partial rescue of V1V2 mutant infectivity by HIV-1 cell-cell transmission supports the domain's exceptional capacity for sequence variation. Retrovirology 11 : 75.

39. EganMA, CarruthLM, RowellJF, YuX, SilicianoRF (1996) Human immunodeficiency virus type 1 envelope protein endocytosis mediated by a highly conserved intrinsic internalization signal in the cytoplasmic domain of gp41 is suppressed in the presence of the Pr55gag precursor protein. J Virol 70 : 6547–6556.

40. YusteE, ReevesJD, DomsRW, DesrosiersRC (2004) Modulation of Env content in virions of simian immunodeficiency virus: correlation with cell surface expression and virion infectivity. J Virol 78 : 6775–6785.

41. PlattEJ, DurninJP, KabatD (2005) Kinetic factors control efficiencies of cell entry, efficacies of entry inhibitors, and mechanisms of adaptation of human immunodeficiency virus. J Virol 79 : 4347–4356.

42. PlattEJ, KozakSL, DurninJP, HopeTJ, KabatD (2010) 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 84 : 3106–3110.

43. MoorePL, RanchobeN, LambsonBE, GrayES, CaveE, et al. (2009) Limited neutralizing antibody specificities drive neutralization escape in early HIV-1 subtype C infection. PLoS Pathog 5: e1000598.

44. RaoM, PeachmanKK, KimJ, GaoG, AlvingCR, et al. (2013) HIV-1 Variable Loop 2 and its Importance in HIV-1 Infection and Vaccine Development. Curr HIV Res 11 : 427–438.

45. Los Alamos HIV database: HIV-1/SIVcpz curated alignment 2013.

46. WalkerLM, PhogatSK, Chan-HuiPY, WagnerD, PhungP, et al. (2009) Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target. Science 326 : 285–289.

47. WibmerCK, BhimanJN, GrayES, TumbaN, Abdool KarimSS, et al. (2013) Viral escape from HIV-1 neutralizing antibodies drives increased plasma neutralization breadth through sequential recognition of multiple epitopes and immunotypes. PLoS Pathog 9: e1003738.

48. WuX, ChangelaA, O'DellS, SchmidtSD, PanceraM, et al. (2011) Immunotypes of a Quaternary Site of HIV-1 Vulnerability and Their Recognition by Antibodies. J Virol 85 : 4578–4585.

49. LuJ, DeeksSG, HohR, BeattyG, KuritzkesBA, et al. (2006) Rapid emergence of enfuvirtide resistance in HIV-1-infected patients: results of a clonal analysis. J Acquir Immune Defic Syndr 43 : 60–64.

50. ReevesJD, LeeFH, MiamidianJL, JabaraCB, JuntillaMM, et al. (2005) Enfuvirtide resistance mutations: impact on human immunodeficiency virus envelope function, entry inhibitor sensitivity, and virus neutralization. J Virol 79 : 4991–4999.

51. EckertDM, KimPS (2001) Mechanisms of viral membrane fusion and its inhibition. Annu Rev Biochem 70 : 777–810.

52. RisseladaHJ, GrubmullerH (2012) How SNARE molecules mediate membrane fusion: recent insights from molecular simulations. Curr Opin Struct Biol 22 : 187–196.

53. ChernomordikLV, KozlovMM (2008) Mechanics of membrane fusion. Nat Struct Mol Biol 15 : 675–683.

54. LiuW, ParpuraV (2010) SNAREs: could they be the answer to an energy landscape riddle in exocytosis? ScientificWorldJournal 10 : 1258–1268.

55. GrafmullerA, ShillcockJ, LipowskyR (2009) The fusion of membranes and vesicles: pathway and energy barriers from dissipative particle dynamics. Biophys J 96 : 2658–2675.

56. MagnusC, RegoesRR (2011) Restricted occupancy models for neutralization of HIV virions and populations. J Theor Biol 283 : 192–202.

57. HaimH, StrackB, KassaA, MadaniN, WangL, et al. (2011) Contribution of Intrinsic Reactivity of the HIV-1 Envelope Glycoproteins to CD4-Independent Infection and Global Inhibitor Sensitivity. PLoS Pathog 7: e1002101.

58. Munro JB, Gorman J, Ma X, Zhou Z, Arthos J, et al.. (2014) Conformational dynamics of single HIV-1 envelope trimers on the surface of native virions. Science.

59. WhiteTA, BartesaghiA, BorgniaMJ, MeyersonJR, de la CruzMJ, et al. (2010) Molecular architectures of trimeric SIV and HIV-1 envelope glycoproteins on intact viruses: strain-dependent variation in quaternary structure. PLoS Pathog 6: e1001249.

60. HoSH, TascaS, ShekL, LiA, GettieA, et al. (2007) Coreceptor switch in R5-tropic simian/human immunodeficiency virus-infected macaques. J Virol 81 : 8621–8633.

61. MohrmannR, de WitH, VerhageM, NeherE, SorensenJB (2010) Fast vesicle fusion in living cells requires at least three SNARE complexes. Science 330 : 502–505.

62. ShiL, ShenQT, KielA, WangJ, WangHW, et al. (2012) SNARE proteins: one to fuse and three to keep the nascent fusion pore open. Science 335 : 1355–1359.

63. MagnusC, BrandenbergOF, RusertP, TrkolaA, RegoesRR (2013) Mathematical models: A key to understanding HIV envelope interactions? J Immunol Methods 398–399 : 1–18.

64. BourinbaiarAS (1994) The ratio of defective HIV-1 particles to replication-competent infectious virions. Acta Virol 38 : 59–61.

65. PoignardP, MoulardM, GolezE, VivonaV, FrantiM, 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.

66. SalzwedelK, BergerEA (2000) Cooperative subunit interactions within the oligomeric envelope glycoprotein of HIV-1: functional complementation of specific defects in gp120 and gp41. Proc Natl Acad Sci U S A 97 : 12794–12799.

67. RusertP, KrarupA, MagnusC, BrandenbergOF, WeberJ, et al. (2011) Interaction of the gp120 V1V2 loop with a neighboring gp120 unit shields the HIV envelope trimer against cross-neutralizing antibodies. J Exp Med 208 : 1419–1433.

68. MagnusC, RegoesRR (2010) Estimating the Stoichiometry of HIV Neutralization. PLoS Comput Biol 6: e1000713.

69. FangQ, LindauM (2014) How Could SNARE Proteins Open a Fusion Pore? Physiology (Bethesda) 29 : 278–285.

70. MarkosyanRM, CohenFS, MelikyanGB (2003) HIV-1 envelope proteins complete their folding into six-helix bundles immediately after fusion pore formation. Mol Biol Cell 14 : 926–938.

71. LiF, PincetF, PerezE, EngWS, MeliaTJ, et al. (2007) Energetics and dynamics of SNAREpin folding across lipid bilayers. Nat Struct Mol Biol 14 : 890–896.

72. LiuW, MontanaV, ParpuraV, MohideenU (2009) Single Molecule Measurements of Interaction Free Energies Between the Proteins Within Binary and Ternary SNARE Complexes. J Nanoneurosci 1 : 120–129.

73. GaoY, ZormanS, GundersenG, XiZ, MaL, et al. (2012) Single reconstituted neuronal SNARE complexes zipper in three distinct stages. Science 337 : 1340–1343.

74. SinhaR, AhmedS, JahnR, KlingaufJ (2011) Two synaptobrevin molecules are sufficient for vesicle fusion in central nervous system synapses. Proc Natl Acad Sci U S A 108 : 14318–14323.

75. MarkinVS, AlbanesiJP (2002) Membrane fusion: stalk model revisited. Biophys J 82 : 693–712.

76. KuzminPI, ZimmerbergJ, ChizmadzhevYA, CohenFS (2001) A quantitative model for membrane fusion based on low-energy intermediates. Proc Natl Acad Sci U S A 98 : 7235–7240.

77. KozlovMM, ChernomordikLV (1998) A mechanism of protein-mediated fusion: coupling between refolding of the influenza hemagglutinin and lipid rearrangements. Biophys J 75 : 1384–1396.

78. WiederholdK, FasshauerD (2009) Is assembly of the SNARE complex enough to fuel membrane fusion? J Biol Chem 284 : 13143–13152.

79. SpearM, GuoJ, WuY (2012) The trinity of the cortical actin in the initiation of HIV-1 infection. Retrovirology 9 : 45.

80. WeiX, DeckerJM, LiuH, ZhangZ, AraniRB, et al. (2002) Emergence of resistant human immunodeficiency virus type 1 in patients receiving fusion inhibitor (T-20) monotherapy. Antimicrob Agents Chemother 46 : 1896–1905.

81. MoorePL, RanchobeN, LambsonBE, GrayES, CaveE, et al. (2009) Limited neutralizing antibody specificities drive neutralization escape in early HIV-1 subtype C infection. PLoS Pathog 5: e1000598.

82. WildC, GreenwellT, MatthewsT (1993) A synthetic peptide from HIV-1 gp41 is a potent inhibitor of virus-mediated cell-cell fusion. AIDS Res Hum Retroviruses 9 : 1051–1053.

83. YangX, KurtevaS, LeeS, SodroskiJ (2005) Stoichiometry of antibody neutralization of human immunodeficiency virus type 1. J Virol 79 : 3500–3508.

84. Team RC (2013) R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing.

85. MannAM, RusertP, BerlingerL, KusterH, GunthardHF, et al. (2009) HIV sensitivity to neutralization is determined by target and virus producer cell properties. AIDS 23 : 1659–1667.