1887

Abstract

HIV-1 passage in cell culture in the presence of chemokine receptor antagonists can result in selection of viruses with mutations that confer resistance to these inhibitors. In the present study, we examined the effect of HIV-1 mutations that confer resistance to CXCR4 antagonists on envelope (Env) sensitivity to neutralizing antibodies (NAbs). Serial passage of CXCR4-tropic HIV-1 NL4-3 in PM1/CCR5 cells under CXCR4 antagonists KRH-3955, AMD3100 and AMD070 yielded two KRH-3955-resistant, one AMD3100-resistant and one AMD070-resistant viruses. These viruses had multiple mutations including the Env gp120 V3 region. The majority of viruses having these CXCR4 antagonist-resistant Envs showed higher sensitivity to NAbs 447-52D, b12 and 2F5 targeting the V3 region, the gp120 CD4-binding site and the gp41 membrane proximal region, respectively, compared to NL4-3 WT virus. Recombinant NL4-3 viruses with the V3-coding region replaced with those derived from the CXCR4 antagonist-resistant viruses showed increased sensitivity to NAbs b12, 2F5 and 447-52D. Molecular dynamics simulations of Env gp120 outer domains predicted that the V3 mutations increased levels of fluctuations at the tip and stem of the V3 loop. These results indicate that mutations in the V3-coding region that result in loss of viral sensitivity to CXCR4 antagonists increase viral sensitivity to NAbs, providing insights into our understanding of the interplay of viral Env accessibility to chemokine receptors and sensitivity to NAbs.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.000536
2016-09-01
2019-10-19
Loading full text...

Full text loading...

/deliver/fulltext/jgv/97/9/2427.html?itemId=/content/journal/jgv/10.1099/jgv.0.000536&mimeType=html&fmt=ahah

References

  1. Adachi A., Gendelman H. E., Koenig S., Folks T., Willey R., Rabson A., Martin M. A..( 1986;). Production of acquired immunodeficiency syndrome-associated retrovirus in human and nonhuman cells transfected with an infectious molecular clone. . J Virol 59: 284–291.[PubMed]
    [Google Scholar]
  2. Barbas C. F., Björling E., Chiodi F., Dunlop N., Cababa D., Jones T. M., Zebedee S. L., Persson M. A., Nara P. L., Norrby E..( 1992;). Recombinant human Fab fragments neutralize human type 1 immunodeficiency virus in vitro. . Proc Natl Acad Sci U S A 89: 9339–9343. [CrossRef] [PubMed]
    [Google Scholar]
  3. Berro R., Sanders R. W., Lu M., Klasse P. J., Moore J. P..( 2009;). Two HIV-1 variants resistant to small molecule CCR5 inhibitors differ in how they use CCR5 for entry. . PLoS Pathog 5: e1000548. [CrossRef] [PubMed]
    [Google Scholar]
  4. Björndal A., Deng H., Jansson M., Fiore J. R., Colognesi C., Karlsson A., Albert J., Scarlatti G., Littman D. R., Fenyö E. M..( 1997;). Coreceptor usage of primary human immunodeficiency virus type 1 isolates varies according to biological phenotype. . J Virol 71: 7478–7487.[PubMed]
    [Google Scholar]
  5. Buchacher A., Predl R., Strutzenberger K., Steinfellner W., Trkola A., Purtscher M., Gruber G., Tauer C., Steindl F., Jungbauer A..( 1994;). 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: 359–369. [CrossRef] [PubMed]
    [Google Scholar]
  6. Burton D. R., Barbas C. F., Persson M. A., Koenig S., Chanock R. M., Lerner R. A..( 1991;). 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 88: 10134–10137. [CrossRef] [PubMed]
    [Google Scholar]
  7. Burton D. R., Pyati J., Koduri R., Sharp S. J., Thornton G. B., Parren P. W., Sawyer L. S., Hendry R. M., Dunlop N. et al.( 1994;). Efficient neutralization of primary isolates of HIV-1 by a recombinant human monoclonal antibody. . Science 266: 1024–1027. [CrossRef] [PubMed]
    [Google Scholar]
  8. Cardozo T., Kimura T., Philpott S., Weiser B., Burger H., Zolla-Pazner S..( 2007;). Structural basis for coreceptor selectivity by the HIV type 1 V3 loop. . AIDS Res Hum Retroviruses 23: 415–426. [CrossRef] [PubMed]
    [Google Scholar]
  9. Case D. A., Darden T. A., Cheatham T. E. III, Simmerling C. L., Wang J., Duke R. E., Luo R., Walker R. C., Zhang W. et al.( 2010;). AMBER11. San Francisco, USA:: University of California;.
    [Google Scholar]
  10. Crawford J. M., Earl P. L., Moss B., Reimann K. A., Wyand M. S., Manson K. H., Bilska M., Zhou J. T., Pauza C. D. et al.( 1999;). Characterization of primary isolate-like variants of simian-human immunodeficiency virus. . J Virol 73: 10199–10207.[PubMed]
    [Google Scholar]
  11. De Clercq E., Yamamoto N., Pauwels R., Balzarini J., Witvrouw M., De Vreese K., Debyser Z., Rosenwirth B., Peichl P., Datema R..( 1994;). Highly potent and selective inhibition of human immunodeficiency virus by the bicyclam derivative JM3100. . Antimicrob Agents Chemother 38: 668–674. [CrossRef] [PubMed]
    [Google Scholar]
  12. De Jong J. J., De Ronde A., Keulen W., Tersmette M., Goudsmit J..( 1992;). Minimal requirements for the human immunodeficiency virus type 1 V3 domain to support the syncytium-inducing phenotype: analysis by single amino acid substitution. . J Virol 66: 6777–6780.[PubMed]
    [Google Scholar]
  13. de Vreese K., Kofler-Mongold V., Leutgeb C., Weber V., Vermeire K., Schacht S., Anné J., de Clercq E., Datema R., Werner G..( 1996;). The molecular target of bicyclams, potent inhibitors of human immunodeficiency virus replication. . J Virol 70: 689–696.[PubMed]
    [Google Scholar]
  14. Dodson G. G., Lane D. P., Verma C. S..( 2008;). Molecular simulations of protein dynamics: new windows on mechanisms in biology. . EMBO Rep 9: 144–150. [CrossRef] [PubMed]
    [Google Scholar]
  15. Etemad-Moghadam B., Sun Y., Nicholson E. K., Karlsson G. B., Schenten D., Sodroski J..( 1999;). Determinants of neutralization resistance in the envelope glycoproteins of a simian-human immunodeficiency virus passaged in vivo. . J Virol 73: 8873–8879.[PubMed]
    [Google Scholar]
  16. Fouchier R. A., Groenink M., Kootstra N. A., Tersmette M., Huisman H. G., Miedema F., Schuitemaker H..( 1992;). Phenotype-associated sequence variation in the third variable domain of the human immunodeficiency virus type 1 gp120 molecule. . J Virol 66: 3183–3187.[PubMed]
    [Google Scholar]
  17. Freed E. O., Englund G., Martin M. A..( 1995;). Role of the basic domain of human immunodeficiency virus type 1 matrix in macrophage infection. . J Virol 69: 3949–3954.[PubMed]
    [Google Scholar]
  18. Gerlach L. O., Skerlj R. T., Bridger G. J., Schwartz T. W..( 2001;). Molecular interactions of cyclam and bicyclam non-peptide antagonists with the CXCR4 chemokine receptor. . J Biol Chem 276: 14153–14160. [CrossRef] [PubMed]
    [Google Scholar]
  19. Gorny M. K., Conley A. J., Karwowska S., Buchbinder A., Xu J. Y., Emini E. A., Koenig S., Zolla-Pazner S..( 1992;). Neutralization of diverse human immunodeficiency virus type 1 variants by an anti-V3 human monoclonal antibody. . J Virol 66: 7538–7542.[PubMed]
    [Google Scholar]
  20. Gulick R. M., Lalezari J., Goodrich J., Clumeck N., DeJesus E., Horban A., Nadler J., Clotet B., Karlsson A. et al.( 2008;). Maraviroc for previously treated patients with R5 HIV-1 infection. . N Engl J Med 359: 1429–1441. [CrossRef] [PubMed]
    [Google Scholar]
  21. Hioe C. E., Wrin T., Seaman M. S., Yu X., Wood B., Self S., Williams C., Gorny M. K., Zolla-Pazner S..( 2010;). Anti-V3 monoclonal antibodies display broad neutralizing activities against multiple HIV-1 subtypes. . PLoS One 5: e10254. [CrossRef] [PubMed]
    [Google Scholar]
  22. Ho S. N., Hunt H. D., Horton R. M., Pullen J. K., Pease L. R..( 1989;). Site-directed mutagenesis by overlap extension using the polymerase chain reaction. . Gene 77: 51–59. [CrossRef] [PubMed]
    [Google Scholar]
  23. Huang C. C., Tang M., Zhang M. Y., Majeed S., Montabana E., Stanfield R. L., Dimitrov D. S., Korber B., Sodroski J. et al.( 2005;). Structure of a V3-containing HIV-1 gp120 core. . Science 310: 1025–1028. [CrossRef] [PubMed]
    [Google Scholar]
  24. Huang C. C., Lam S. N., Acharya P., Tang M., Xiang S. H., Hussan S. S., Stanfield R. L., Robinson J., Sodroski J. et al.( 2007;). Structures of the CCR5 N terminus and of a tyrosine-sulfated antibody with HIV-1 gp120 and CD4. . Science 317: 1930–1934. [CrossRef] [PubMed]
    [Google Scholar]
  25. Jorgensen W. L., Chandrasekhar J., Madura J. D., Impey R. W., Klein M. L..( 1983;). Comparison of simple potential functions for simulating liquid water. . J Chem Phys 79: 926. [CrossRef]
    [Google Scholar]
  26. Kanbara K., Sato S., Tanuma J., Tamamura H., Gotoh K., Yoshimori M., Kanamoto T., Kitano M., Fujii N., Nakashima H..( 2001;). Biological and genetic characterization of a human immunodeficiency virus strain resistant to CXCR4 antagonist T134. . AIDS Res Hum Retroviruses 17: 615–622. [CrossRef] [PubMed]
    [Google Scholar]
  27. Karplus M., Kuriyan J..( 2005;). Molecular dynamics and protein function. . Proc Natl Acad Sci U S A 102: 6679–6685. [CrossRef] [PubMed]
    [Google Scholar]
  28. Koch M., Pancera M., Kwong P. D., Kolchinsky P., Grundner C., Wang L., Hendrickson W. A., Sodroski J., Wyatt R..( 2003;). Structure-based, targeted deglycosylation of HIV-1 gp120 and effects on neutralization sensitivity and antibody recognition. . Virology 313: 387–400. [CrossRef] [PubMed]
    [Google Scholar]
  29. Kuhmann S. E., Pugach P., Kunstman K. J., Taylor J., Stanfield R. L., Snyder A., Strizki J. M., Riley J., Baroudy B. M. et al.( 2004;). Genetic and phenotypic analyses of human immunodeficiency virus type 1 escape from a small-molecule CCR5 inhibitor. . J Virol 78: 2790–2807. [CrossRef] [PubMed]
    [Google Scholar]
  30. Kuwata T., Takaki K., Yoshimura K., Enomoto I., Wu F., Ourmanov I., Hirsch V. M., Yokoyama M., Sato H., Matsushita S..( 2013;). Conformational epitope consisting of the V3 and V4 loops as a target for potent and broad neutralization of simian immunodeficiency viruses. . J Virol 87: 5424–5436. [CrossRef] [PubMed]
    [Google Scholar]
  31. Li Y., Cleveland B., Klots I., Travis B., Richardson B. A., Anderson D., Montefiori D., Polacino P., Hu S. L..( 2008;). 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. [CrossRef] [PubMed]
    [Google Scholar]
  32. Li Y., O'Dell S., Walker L. M., Wu X., Guenaga J., Feng Y., Schmidt S. D., McKee K., Louder M. K. et al.( 2011;). Mechanism of neutralization by the broadly neutralizing HIV-1 monoclonal antibody VRC01. . J Virol 85: 8954–8967. [CrossRef] [PubMed]
    [Google Scholar]
  33. Lindorff-Larsen K., Piana S., Palmo K., Maragakis P., Klepeis J. L., Dror R. O., Shaw D. E..( 2010;). Improved side-chain torsion potentials for the Amber ff99SB protein force field. . Proteins 78: 1950–1958. [CrossRef] [PubMed]
    [Google Scholar]
  34. Maeda Y., Yusa K., Harada S..( 2008;). Altered sensitivity of an R5X4 HIV-1 strain 89.6 to coreceptor inhibitors by a single amino acid substitution in the V3 region of gp120. . Antiviral Res 77: 128–135. [CrossRef] [PubMed]
    [Google Scholar]
  35. Marozsan A. J., Kuhmann S. E., Morgan T., Herrera C., Rivera-Troche E., Xu S., Baroudy B. M., Strizki J., Moore J. P..( 2005;). Generation and properties of a human immunodeficiency virus type 1 isolate resistant to the small molecule CCR5 inhibitor, SCH-417690 (SCH-D). . Virology 338: 182–199. [CrossRef] [PubMed]
    [Google Scholar]
  36. Mascola J. R., Lewis M. G., Stiegler G., Harris D., VanCott T. C., Hayes D., Louder M. K., Brown C. R., Sapan C. et al.( 1999;). Protection of macaques against pathogenic simian/human immunodeficiency virus 89.6PD by passive transfer of neutralizing antibodies. . J Virol 73: 4009–4018.[PubMed]
    [Google Scholar]
  37. Moncunill G., Armand-Ugón M., Clotet-Codina I., Pauls E., Ballana E., Llano A., Romagnoli B., Vrijbloed J. W., Gombert F. O. et al.( 2008;). Anti-HIV activity and resistance profile of the CXC chemokine receptor 4 antagonist POL3026. . Mol Pharmacol 73: 1264–1273. [CrossRef] [PubMed]
    [Google Scholar]
  38. Moyle G., DeJesus E., Boffito M., Wong R. S., Gibney C., Badel K., MacFarland R., Calandra G., Bridger G., Becker S..X4 Antagonist Concept Trial Study Team( 2009;). Proof of activity with AMD11070, an orally bioavailable inhibitor of CXCR4-tropic HIV type 1. . Clin Infect Dis 48: 798–805. [CrossRef] [PubMed]
    [Google Scholar]
  39. Murakami T., Nakajima T., Koyanagi Y., Tachibana K., Fujii N., Tamamura H., Yoshida N., Waki M., Matsumoto A. et al.( 1997;). A small molecule CXCR4 inhibitor that blocks T cell line-tropic HIV-1 infection. . J Exp Med 186: 1389–1393. [CrossRef] [PubMed]
    [Google Scholar]
  40. Murakami T., Zhang T.-Y., Koyanagi Y., Tanaka Y., Kim J., Suzuki Y., Minoguchi S., Tamamura H., Waki M. et al.( 2002;). Inhibitory mechanism of the CXCR4 antagonist T22 against human immunodeficiency virus type 1 infection. . J Virol 76: 933. [CrossRef]
    [Google Scholar]
  41. Murakami T., Kumakura S., Yamazaki T., Tanaka R., Hamatake M., Okuma K., Huang W., Toma J., Komano J. et al.( 2009;). The novel CXCR4 antagonist KRH-3955 is an orally bioavailable and extremely potent inhibitor of human immunodeficiency virus type 1 infection: comparative studies with AMD3100. . Antimicrob Agents Chemother 53: 2940–2948. [CrossRef] [PubMed]
    [Google Scholar]
  42. Naganawa S., Yokoyama M., Shiino T., Suzuki T., Ishigatsubo Y., Ueda A., Shirai A., Takeno M., Hayakawa S. et al.( 2008;). Net positive charge of HIV-1 CRF01_AE V3 sequence regulates viral sensitivity to humoral immunity. . PLoS One 3: e3206. [CrossRef] [PubMed]
    [Google Scholar]
  43. Nakashima H., Masuda M., Murakami T., Koyanagi Y., Matsumoto A., Fujii N., Yamamoto N..( 1992;). Anti-human immunodeficiency virus activity of a novel synthetic peptide, T22 ([Tyr-5,12, Lys-7]polyphemusin II): a possible inhibitor of virus-cell fusion. . Antimicrob Agents Chemother 36: 1249–1255. [CrossRef] [PubMed]
    [Google Scholar]
  44. Nakasone T., Kumakura S., Yamamoto M., Murakami T., Yamamoto N..( 2013;). Single oral administration of the novel CXCR4 antagonist, KRH-3955, induces an efficient and long-lasting increase of white blood cell count in normal macaques, and prevents CD4 depletion in SHIV-infected macaques: a preliminary study. . Med Microbiol Immunol 202: 175–182. [CrossRef] [PubMed]
    [Google Scholar]
  45. Ode H., Nakashima M., Kitamura S., Sugiura W., Sato H..( 2012;). Molecular dynamics simulation in virus research. . Front Microbiol 3: 258. [CrossRef] [PubMed]
    [Google Scholar]
  46. Ogert R. A., Lee M. K., Ross W., Buckler-White A., Martin M. A., Cho M. W..( 2001;). N-linked glycosylation sites adjacent to and within the V1/V2 and the V3 loops of dualtropic human immunodeficiency virus type 1 isolate DH12 gp120 affect coreceptor usage and cellular tropism. . J Virol 75: 5998–6006. [CrossRef] [PubMed]
    [Google Scholar]
  47. Platt E. J., Wehrly K., Kuhmann S. E., Chesebro B., Kabat D..( 1998;). Effects of CCR5 and CD4 cell surface concentrations on infections by macrophagetropic isolates of human immunodeficiency virus type 1. . J Virol 72: 2855–2864.[PubMed]
    [Google Scholar]
  48. Platt E. J., Bilska M., Kozak S. L., Kabat D., Montefiori D. C..( 2009;). 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. . J Virol 83: 8289–8292. [CrossRef] [PubMed]
    [Google Scholar]
  49. Polzer S., Müller H., Schreiber M..( 2009;). Effects of mutations on HIV-1 infectivity and neutralization involving the conserved NNNT amino acid sequence in the gp120 V3 loop. . FEBS Lett 583: 1201–1206. [CrossRef] [PubMed]
    [Google Scholar]
  50. Pugach P., Marozsan A. J., Ketas T. J., Landes E. L., Moore J. P., Kuhmann S. E..( 2007;). HIV-1 clones resistant to a small molecule CCR5 inhibitor use the inhibitor-bound form of CCR5 for entry. . Virology 361: 212–228. [CrossRef] [PubMed]
    [Google Scholar]
  51. Pugach P., Ketas T. J., Michael E., Moore J. P..( 2008;). Neutralizing antibody and anti-retroviral drug sensitivities of HIV-1 isolates resistant to small molecule CCR5 inhibitors. . Virology 377: 401–407. [CrossRef] [PubMed]
    [Google Scholar]
  52. Purtscher M., Trkola A., Gruber G., Buchacher A., Predl R., Steindl F., Tauer C., Berger R., Barrett N., Jungbauer A..( 1994;). A broadly neutralizing human monoclonal antibody against gp41 of human immunodeficiency virus type 1. . AIDS Res Hum Retroviruses 10: 1651–1658. [CrossRef] [PubMed]
    [Google Scholar]
  53. Purtscher M., Trkola A., Grassauer A., Schulz P. M., Klima A., Döpper S., Gruber G., Buchacher A., Muster T., Katinger H..( 1996;). Restricted antigenic variability of the epitope recognized by the neutralizing gp41 antibody 2F5. . AIDS 10: 587–593. [CrossRef] [PubMed]
    [Google Scholar]
  54. Reeves J. D., Lee F. H., Miamidian J. L., Jabara C. B., Juntilla M. M., Doms R. W., Robert W..( 2005;). Enfuvirtide resistance mutations: impact on human immunodeficiency virus envelope function, entry inhibitor sensitivity, and virus neutralization. . J Virol 79: 4991–4999. [CrossRef] [PubMed]
    [Google Scholar]
  55. Roben P., Moore J. P., Thali M., Sodroski J., Barbas C. F., Burton D. R..( 1994;). 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 68: 4821–4828.[PubMed]
    [Google Scholar]
  56. Rosenkilde M. M., Gerlach L. O., Hatse S., Skerlj R. T., Schols D., Bridger G. J., Schwartz T. W..( 2007;). Molecular mechanism of action of monocyclam versus bicyclam non-peptide antagonists in the CXCR4 chemokine receptor. . J Biol Chem 282: 27354–27365. [CrossRef] [PubMed]
    [Google Scholar]
  57. Ryckaert J.-P., Ciccotti G., Berendsen H. J..( 1977;). Numerical integration of the cartesian equations of motion of a system with constraints: molecular dynamics of n-alkanes. . J Comput Phys 23: 327–341. [CrossRef]
    [Google Scholar]
  58. Salomon A., Krachmarov C., Lai Z., Honnen W., Zingman B. S., Sarlo J., Gorny M. K., Zolla-Pazner S., Robinson J. E., Pinter A..( 2014;). Specific sequences commonly found in the V3 domain of HIV-1 subtype C isolates affect the overall conformation of native Env and induce a neutralization-resistant phenotype independent of V1/V2 masking. . Virology 448: 363–374. [CrossRef] [PubMed]
    [Google Scholar]
  59. Schols D., Struyf S., Van Damme J., Esté J. A., Henson G., De Clercq E., Damme J. V.( 1997;). Inhibition of T-tropic HIV strains by selective antagonization of the chemokine receptor CXCR4. . J Exp Med 186: 1383–1388. [CrossRef] [PubMed]
    [Google Scholar]
  60. Schols D., Esté J. A., Cabrera C., De Clercq E..( 1998;). T-cell-line-tropic human immunodeficiency virus type 1 that is made resistant to stromal cell-derived factor 1α contains mutations in the envelope gp120 but does not show a switch in coreceptor use. . J Virol 72: 4032–4037.[PubMed]
    [Google Scholar]
  61. Strizki J. M., Xu S., Wagner N. E., Wojcik L., Liu J., Hou Y., Endres M., Palani A., Shapiro S. et al.( 2001;). SCH-C (SCH 351125), an orally bioavailable, small molecule antagonist of the chemokine receptor CCR5, is a potent inhibitor of HIV-1 infection in vitro and in vivo. . Proc Natl Acad Sci U S A 98: 12718–12723. [CrossRef] [PubMed]
    [Google Scholar]
  62. Strizki J. M., Tremblay C., Xu S., Wojcik L., Wagner N., Gonsiorek W., Hipkin R. W., Chou C. C., Pugliese-Sivo C. et al.( 2005;). Discovery and characterization of vicriviroc (SCH 417690), a CCR5 antagonist with potent activity against human immunodeficiency virus type 1. . Antimicrob Agents Chemother 49: 4911–4919. [CrossRef] [PubMed]
    [Google Scholar]
  63. Sullivan N., Sun Y., Sattentau Q., Thali M., Wu D., Denisova G., Gershoni J., Robinson J., Moore J., Sodroski J..( 1998;). CD4-induced conformational changes in the human immunodeficiency virus type 1 gp120 glycoprotein: consequences for virus entry and neutralization. . J Virol 72: 4694–4703.[PubMed]
    [Google Scholar]
  64. Takeuchi Y., McClure M. O., Pizzato M..( 2008;). Identification of gammaretroviruses constitutively released from cell lines used for human immunodeficiency virus research. . J Virol 82: 12585–12588. [CrossRef] [PubMed]
    [Google Scholar]
  65. Tamamura H., Xu Y., Hattori T., Zhang X., Arakaki R., Kanbara K., Omagari A., Otaka A., Ibuka T. et al.( 1998;). A low-molecular-weight inhibitor against the chemokine receptor CXCR4: a strong anti-HIV peptide T140. . Biochem Biophys Res Commun 253: 877–882. [CrossRef] [PubMed]
    [Google Scholar]
  66. Thali M., Moore J. P., Furman C., Charles M., Ho D. D., Robinson J., Sodroski J..( 1993;). Characterization of conserved human immunodeficiency virus type 1 gp120 neutralization epitopes exposed upon gp120-CD4 binding. . J Virol 67: 3978–3988.[PubMed]
    [Google Scholar]
  67. Trkola A., Purtscher M., Muster T., Ballaun C., Buchacher A., Sullivan N., Srinivasan K., Sodroski J., Moore J. P., Katinger H..( 1996;). Human monoclonal antibody 2G12 defines a distinctive neutralization epitope on the gp120 glycoprotein of human immunodeficiency virus type 1. . J Virol 70: 1100–1108.[PubMed]
    [Google Scholar]
  68. Trkola A., Kuhmann S. E., Strizki J. M., Maxwell E., Ketas T., Morgan T., Pugach P., Xu S., Wojcik L. et al.( 2002;). HIV-1 escape from a small molecule, CCR5-specific entry inhibitor does not involve CXCR4 use. . Proc Natl Acad Sci U S A 99: 395–400. [CrossRef] [PubMed]
    [Google Scholar]
  69. Tsamis F., Gavrilov S., Kajumo F., Seibert C., Kuhmann S., Ketas T., Trkola A., Palani A., Clader J. W. et al.( 2003;). Analysis of the mechanism by which the small-molecule CCR5 antagonists SCH-351125 and SCH-350581 inhibit human immunodeficiency virus type 1 entry. . J Virol 77: 5201–5208. [CrossRef] [PubMed]
    [Google Scholar]
  70. Walker L. M., Phogat S. K., Chan-Hui P. Y., Wagner D., Phung P., Goss J. L., Wrin T., Simek M. D., Fling S. et al.( 2009;). Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target. . Science 326: 285–289. [CrossRef] [PubMed]
    [Google Scholar]
  71. Wang W., Nie J., Prochnow C., Truong C., Jia Z., Wang S., Chen X. S., Wang Y..( 2013;). A systematic study of the N-glycosylation sites of HIV-1 envelope protein on infectivity and antibody-mediated neutralization. . Retrovirology 10: 14. [CrossRef]
    [Google Scholar]
  72. Wei X., Decker J. M., Liu H., Zhang Z., Arani R. B., Kilby J. M., Saag M. S., Wu X., Shaw G. M., Kappes J. C..( 2002;). Emergence of resistant human immunodeficiency virus type 1 in patients receiving fusion inhibitor (T-20) monotherapy. . Antimicrob Agents Chemother 46: 1896–1905. [CrossRef] [PubMed]
    [Google Scholar]
  73. Westby M., Smith-Burchnell C., Mori J., Lewis M., Mosley M., Stockdale M., Dorr P., Ciaramella G., Perros M..( 2007;). Reduced maximal inhibition in phenotypic susceptibility assays indicates that viral strains resistant to the CCR5 antagonist maraviroc utilize inhibitor-bound receptor for entry. . J Virol 81: 2359–2371. [CrossRef] [PubMed]
    [Google Scholar]
  74. Wilen C. B., Tilton J. C., Doms R. W..( 2012;). HIV: cell binding and entry. . Cold Spring Harb Perspect Med 2: a006866. [CrossRef] [PubMed]
    [Google Scholar]
  75. Wu X., Yang Z.-Y., Li Y., Hogerkorp C.-M., Schief W. R., Seaman M. S., Zhou T., Schmidt S. D., Wu L. et al.( 2010;). Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1. . Science 329: 856–861. [CrossRef] [PubMed]
    [Google Scholar]
  76. Wyatt R., Sodroski J..( 1998;). The HIV-1 envelope glycoproteins: fusogens, antigens, and immunogens. . Science 280: 1884–1888. [CrossRef] [PubMed]
    [Google Scholar]
  77. Wyatt R., Moore J., Accola M., Desjardin E., Robinson J., Sodroski J..( 1995;). Involvement of the V1/V2 variable loop structure in the exposure of human immunodeficiency virus type 1 gp120 epitopes induced by receptor binding. . J Virol 69: 5723–5733.[PubMed]
    [Google Scholar]
  78. Wyatt R., Kwong P. D., Desjardins E., Sweet R. W., Robinson J., Hendrickson W. A., Sodroski J. G..( 1998;). The antigenic structure of the HIV gp120 envelope glycoprotein. . Nature 393: 705–711. [CrossRef] [PubMed]
    [Google Scholar]
  79. Xiang S. H., Pacheco B., Bowder D., Yuan W., Sodroski J..( 2013;). Characterization of a dual-tropic human immunodeficiency virus (HIV-1) strain derived from the prototypical X4 isolate HXBc2. . Virology 438: 5–13. [CrossRef] [PubMed]
    [Google Scholar]
  80. Yokoyama M., Naganawa S., Yoshimura K., Matsushita S., Sato H..( 2012;). Structural dynamics of HIV-1 envelope gp120 outer domain with V3 loop. . PLoS One 7: e37530. [CrossRef] [PubMed]
    [Google Scholar]
  81. Yokoyama M., Nomaguchi M., Doi N., Kanda T., Adachi A., Sato H..( 2016;). In silico analysis of HIV-1 Env-gp120 reveals structural bases for viral adaptation in growth-restrictive cells. . Front Microbiol 7: 110. [CrossRef] [PubMed]
    [Google Scholar]
  82. Yoshimura K., Harada S., Boonchawalit S., Kawanami Y., Matsushita S..( 2014;). Impact of maraviroc-resistant and low-CCR5-adapted mutations induced by in vitro passage on sensitivity to anti-envelope neutralizing antibodies. . J Gen Virol 95: 1816–1826. [CrossRef] [PubMed]
    [Google Scholar]
  83. Yuan Y., Yokoyama M., Maeda Y., Terasawa H., Harada S., Sato H., Yusa K..( 2013;). Structure and dynamics of the gp120 V3 loop that confers noncompetitive resistance in R5 HIV-1(JR-FL) to maraviroc. . PLoS One 8: e65115. [CrossRef] [PubMed]
    [Google Scholar]
  84. Zhang P. F., Bouma P., Park E. J., Margolick J. B., Robinson J. E., Zolla-Pazner S., Flora M. N., Quinnan G..( 2002;). A variable region 3 (V3) mutation determines a global neutralization phenotype and CD4-independent infectivity of a human immunodeficiency virus type 1 envelope associated with a broadly cross-reactive, primary virus-neutralizing antibody response. . J Virol 76: 644–655. [CrossRef] [PubMed]
    [Google Scholar]
  85. Zolla-Pazner S., Cohen S. S., Boyd D., Kong X. P., Seaman M., Nussenzweig M., Klein F., Overbaugh J., Totrov M..( 2015;). Structure/function studies involving the V3 region of the HIV-1 envelope delineate multiple factors that affect neutralization sensitivity. . J Virol 90: 636–649. [CrossRef] [PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/jgv.0.000536
Loading
/content/journal/jgv/10.1099/jgv.0.000536
Loading

Data & Media loading...

Supplements

Supplementary File 1

PDF

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error