1887

Abstract

Infection of rhesus macaques with a deglycosylation mutant, Δ5G, derived from SIV239, a pathogenic clone of simian immunodeficiency virus (SIV), led to robust acute-phase viral replication followed by a chronic phase with undetectable viral load. This study examined whether humoral responses in Δ5G-infected animals played any role in the control of infection. Neutralizing antibodies (nAbs) were elicited more efficiently in Δ5G-infected animals than in SIV239-infected animals. However, functional nAb measured by 90 % neutralization was prominent in only two of the five Δ5G-infected animals, and only at 8 weeks post-infection (p.i.), when viral loads were already below 10 copies ml. These results suggest a minimal role for nAbs in the control of the primary infection. In contrast, whilst Ab responses to epitopes localized to the variable loops V1/V2 were detected in all Δ5G-infected animals at 3 weeks p.i., this response was associated with a concomitant reduction in Ab responses to epitopes in gp41 compared with those in SIV239-infected animals. These results suggest that the altered surface glycosylation and/or conformation of viral spikes induce a humoral response against SIV that is distinct from the response induced by SIV239. More interestingly, whereas V1/V2-specific Abs were induced in all animals, these Abs were associated with vigorous Δ5G-specific virion capture ability in only two Δ5G-infected animals that exhibited a functional nAb response. Thus, whereas the deglycosylation mutant infection elicited early virion capture and subsequent nAbs, the responses differed among animals, suggesting the existence of host factors that may influence the functional humoral responses against human immunodeficiency virus/SIV.

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2008-02-01
2019-11-18
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References

  1. Aasa-Chapman, M. M., Holuigue, S., Aubin, K., Wong, M., Jones, N. A., Cornforth, D., Pellegrino, P., Newton, P., Williams, I. & other authors ( 2005; ). Detection of antibody-dependent complement-mediated inactivation of both autologous and heterologous virus in primary human immunodeficiency virus type 1 infection. J Virol 79, 2823–2830.[CrossRef]
    [Google Scholar]
  2. Ahmad, A. & Menezes, J. ( 1996; ). Antibody-dependent cellular cytotoxicity in HIV infections. FASEB J 10, 258–266.
    [Google Scholar]
  3. Benichou, S., Venet, A., Beyer, C., Tiollais, P. & Madaule, P. ( 1993; ). Characterization of B-cell epitopes in the envelope glycoproteins of simian immunodeficiency virus. Virology 194, 870–874.[CrossRef]
    [Google Scholar]
  4. Bontrop, R. E., Otting, N., Niphuis, H., Noort, R., Teeuwsen, V. & Heeney, J. L. ( 1996; ). The role of major histocompatibility complex polymorphisms on SIV infection in rhesus macaques. Immunol Lett 51, 35–38.[CrossRef]
    [Google Scholar]
  5. Burns, D. P. & Desrosiers, R. C. ( 1991; ). Selection of genetic variants of simian immunodeficiency virus in persistently infected rhesus monkeys. J Virol 65, 1843–1854.
    [Google Scholar]
  6. Burton, D. R., Desrosiers, R. C., Doms, R. W., Koff, W. C., Kwong, P. D., Moore, J. P., Nabel, G. J., Sodroski, J., Wilson, I. A. & Wyatt, R. T. ( 2004; ). HIV vaccine design and the neutralizing antibody problem. Nat Immunol 5, 233–236.[CrossRef]
    [Google Scholar]
  7. Caffrey, M., Cai, M., Kaufman, J., Stahl, S. J., Wingfield, P. T., Covell, D. G., Gronenborn, A. M. & Clore, G. M. ( 1998; ). Three-dimensional solution structure of the 44 kDa ectodomain of SIV gp41. EMBO J 17, 4572–4584.[CrossRef]
    [Google Scholar]
  8. Cao, J., Bergeron, L., Helseth, E., Thali, M., Repke, H. & Sodroski, J. ( 1993; ). Effects of amino acid changes in the extracellular domain of the human immunodeficiency virus type 1 gp41 envelope glycoprotein. J Virol 67, 2747–2755.
    [Google Scholar]
  9. Chackerian, B., Rudensey, L. M. & Overbaugh, J. ( 1997; ). Specific N-linked and O-linked glycosylation modifications in the envelope V1 domain of simian immunodeficiency virus variants that evolve in the host alter recognition by neutralizing antibodies. J Virol 71, 7719–7727.
    [Google Scholar]
  10. Chen, B., Vogan, E. M., Gong, H., Skehel, J. J., Wiley, D. C. & Harrison, S. C. ( 2005; ). Structure of an unliganded simian immunodeficiency virus gp120 core. Nature 433, 834–841.[CrossRef]
    [Google Scholar]
  11. Cheng-Mayer, C., Brown, A., Harouse, J., Luciw, P. A. & Mayer, A. J. ( 1999; ). Selection for neutralization resistance of the simian/human immunodeficiency virus SHIVSF33A variant in vivo by virtue of sequence changes in the extracellular envelope glycoprotein that modify N-linked glycosylation. J Virol 73, 5294–5300.
    [Google Scholar]
  12. Choi, W. S., Collignon, C., Thiriart, C., Burns, D. P., Stott, E. J., Kent, K. A. & Desrosiers, R. C. ( 1994; ). Effects of natural sequence variation on recognition by monoclonal antibodies neutralize simian immunodeficiency virus infectivity. J Virol 68, 5395–5402.
    [Google Scholar]
  13. Dowling, W., Thompson, E., Badger, C., Mellquist, J. L., Garrison, A. R., Smith, J. M., Paragas, J., Hogan, R. J. & Schmaljohn, C. ( 2007; ). Influences of glycosylation on antigenicity, immunogenicity, and protective efficacy of Ebola virus GP DNA vaccines. J Virol 81, 1821–1837.[CrossRef]
    [Google Scholar]
  14. Draenert, R., Allen, T. M., Liu, Y., Wrin, T., Chappey, C., Verrill, C. L., Sirera, G., Eldridge, R. L., Lahaie, M. P. & other authors ( 2006; ). Constraints on HIV-1 evolution and immunodominance revealed in monozygotic adult twins infected with the same virus. J Exp Med 203, 529–539.[CrossRef]
    [Google Scholar]
  15. Eberle, J., Loussert-Ajaka, I., Brust, S., Zekeng, L., Hauser, P. H., Kaptue, L., Knapp, S., Damond, F., Saragosti, S. & other authors ( 1997; ). Diversity of the immunodominant epitope of gp41 of HIV-1 subtype O and its validity for antibody detection. J Virol Methods 67, 85–91.[CrossRef]
    [Google Scholar]
  16. Forthal, D. N., Landucci, G. & Keenan, B. ( 2001; ). Relationship between antibody-dependent cellular cytotoxicity, plasma HIV type 1 RNA, and CD4+ lymphocyte count. AIDS Res Hum Retroviruses 17, 553–561.[CrossRef]
    [Google Scholar]
  17. Fournillier, A., Wychowski, C., Boucreux, D., Baumert, T. F., Meunier, J. C., Jacobs, D., Muguet, S., Depla, E. & Inchauspe, G. ( 2001; ). Induction of hepatitis C virus E1 envelope protein-specific immune response can be enhanced by mutation of N-glycosylation sites. J Virol 75, 12088–12097.[CrossRef]
    [Google Scholar]
  18. Gnann, J. W., Jr, Nelson, J. A. & Oldstone, M. B. ( 1987; ). Fine mapping of an immunodominant domain in the transmembrane glycoprotein of human immunodeficiency virus. J Virol 61, 2639–2641.
    [Google Scholar]
  19. Haigwood, N. L. & Stamatatos, L. ( 2003; ). Role of neutralizing antibodies in HIV infection. AIDS 17 (Suppl. 4), S67–S71.[CrossRef]
    [Google Scholar]
  20. Hangartner, L., Zellweger, R. M., Giobbi, M., Weber, J., Eschli, B., McCoy, K. D., Harris, N., Recher, M., Zinkernagel, R. M. & Hengartner, H. ( 2006a; ). Nonneutralizing antibodies binding to the surface glycoprotein of lymphocytic choriomeningitis virus reduce early virus spread. J Exp Med 203, 2033–2042.[CrossRef]
    [Google Scholar]
  21. Hangartner, L., Zinkernagel, R. M. & Hengartner, H. ( 2006b; ). Antiviral antibody responses: the two extremes of a wide spectrum. Nat Rev Immunol 6, 231–243.[CrossRef]
    [Google Scholar]
  22. Hasenkrug, K. J., Valenzuela, A., Letts, V. A., Nishio, J., Chesebro, B. & Frankel, W. N. ( 1995; ). Chromosome mapping of Rfv3, a host resistance gene to Friend murine retrovirus. J Virol 69, 2617–2620.
    [Google Scholar]
  23. Hofmann-Lehmann, R., Swenerton, R. K., Liska, V., Leutenegger, C. M., Lutz, H., McClure, H. M. & Ruprecht, R. M. ( 2000; ). Sensitive and robust one-tube real-time reverse transcriptase-polymerase chain reaction to quantify SIV RNA load: comparison of one- versus two-enzyme systems. AIDS Res Hum Retroviruses 16, 1247–1257.[CrossRef]
    [Google Scholar]
  24. Huso, D. L., Narayan, O. & Hart, G. W. ( 1988; ). Sialic acids on the surface of caprine arthritis-encephalitis virus define the biological properties of the virus. J Virol 62, 1974–1980.
    [Google Scholar]
  25. Johnson, W. E., Sanford, H., Schwall, L., Burton, D. R., Parren, P. W., Robinson, J. E. & Desrosiers, R. C. ( 2003; ). Assorted mutations in the envelope gene of simian immunodeficiency virus lead to loss of neutralization resistance against antibodies representing a broad spectrum of specificities. J Virol 77, 9993–10003.[CrossRef]
    [Google Scholar]
  26. Kanari, Y., Clerici, M., Abe, H., Kawabata, H., Trabattoni, D., Caputo, S. L., Mazzotta, F., Fujisawa, H., Niwa, A. & other authors ( 2005; ). Genotypes at chromosome 22q12–13 are associated with HIV-1-exposed but uninfected status in Italians. AIDS 19, 1015–1024.[CrossRef]
    [Google Scholar]
  27. Kent, K. A., Rud, E., Corcoran, T., Powell, C., Thiriart, C., Collignon, C. & Stott, E. J. ( 1992; ). Identification of two neutralizing and 8 non-neutralizing epitopes on simian immunodeficiency virus envelope using monoclonal antibodies. AIDS Res Hum Retroviruses 8, 1147–1151.[CrossRef]
    [Google Scholar]
  28. Kolchinsky, P., Kiprilov, E., Bartley, P., Rubinstein, R. & Sodroski, J. ( 2001; ). Loss of a single N-linked glycan allows CD4-independent human immunodeficiency virus type 1 infection by altering the position of the gp120 V1/V2 variable loops. J Virol 75, 3435–3443.[CrossRef]
    [Google Scholar]
  29. Leonard, C. K., Spellman, M. W., Riddle, L., Harris, R. J., Thomas, J. N. & Gregory, T. J. ( 1990; ). Assignment of intrachain disulfide bonds and characterization of potential glycosylation sites of the type 1 recombinant human immunodeficiency virus envelope glycoprotein (gp120) expressed in Chinese hamster ovary cells. J Biol Chem 265, 10373–10382.
    [Google Scholar]
  30. Lifson, J. D., Rossio, J. L., Arnaout, R., Li, L., Parks, T. L., Schneider, D. K., Kiser, R. F., Coalter, V. J., Walsh, G. & other authors ( 2000; ). Containment of simian immunodeficiency virus infection: cellular immune responses and protection from rechallenge following transient postinoculation antiretroviral treatment. J Virol 74, 2584–2593.[CrossRef]
    [Google Scholar]
  31. Liu, J., Wang, S., Hoxie, J. A., LaBranche, C. C. & Lu, M. ( 2002; ). Mutations that destabilize the gp41 core are determinants for stabilizing the simian immunodeficiency virus-CPmac envelope glycoprotein complex. J Biol Chem 277, 12891–12900.[CrossRef]
    [Google Scholar]
  32. Maerz, A. L., Drummer, H. E., Wilson, K. A. & Poumbourios, P. ( 2001; ). Functional analysis of the disulfide-bonded loop/chain reversal region of human immunodeficiency virus type 1 gp41 reveals a critical role in gp120-gp41 association. J Virol 75, 6635–6644.[CrossRef]
    [Google Scholar]
  33. Means, R. E., Greenough, T. & Desrosiers, R. C. ( 1997; ). Neutralization sensitivity of cell culture-passaged simian immunodeficiency virus. J Virol 71, 7895–7902.
    [Google Scholar]
  34. Miyazawa, M., Nishio, J., Wehrly, K. & Chesebro, B. ( 1992; ). Influence of MHC genes on spontaneous recovery from Friend retrovirus-induced leukemia. J Immunol 148, 644–647.
    [Google Scholar]
  35. Mori, K., Yasutomi, Y., Sawada, S., Villinger, F., Sugama, K., Rosenwith, B., Heeney, J. L., Uberla, K., Yamazaki, S. & other authors ( 2000; ). Suppression of acute viremia by short-term postexposure prophylaxis of simian/human immunodeficiency virus SHIV-RT-infected monkeys with a novel reverse transcriptase inhibitor (GW420867) allows for development of potent antiviral immune responses resulting in efficient containment of infection. J Virol 74, 5747–5753.[CrossRef]
    [Google Scholar]
  36. Mori, K., Yasutomi, Y., Ohgimoto, S., Nakasone, T., Takamura, S., Shioda, T. & Nagai, Y. ( 2001; ). Quintuple deglycosylation mutant of simian immunodeficiency virus SIVmac239 in rhesus macaques: robust primary replication, tightly contained chronic infection, and elicitation of potent immunity against the parental wild-type strain. J Virol 75, 4023–4028.[CrossRef]
    [Google Scholar]
  37. Mori, K., Sugimoto, C., Ohgimoto, S., Nakayama, E. E., Shioda, T., Kusagawa, S., Takebe, Y., Kano, M., Matano, T. & other authors ( 2005; ). Influence of glycosylation on the efficacy of an Env-based vaccine against simian immunodeficiency virus SIVmac239 in a macaque AIDS model. J Virol 79, 10386–10396.[CrossRef]
    [Google Scholar]
  38. Muster, T., Steindl, F., Purtscher, M., Trkola, A., Klima, A., Himmler, G., Ruker, F. & Katinger, H. ( 1993; ). A conserved neutralizing epitope on gp41 of human immunodeficiency virus type 1. J Virol 67, 6642–6647.
    [Google Scholar]
  39. Nishimura, Y., Igarashi, T., Haigwood, N., Sadjadpour, R., Plishka, R. J., Buckler-White, A., Shibata, R. & Martin, M. A. ( 2002; ). Determination of a statistically valid neutralization titer in plasma that confers protection against simian-human immunodeficiency virus challenge following passive transfer of high-titered neutralizing antibodies. J Virol 76, 2123–2130.[CrossRef]
    [Google Scholar]
  40. Nyambi, P. N., Gorny, M. K., Bastiani, L., van der Groen, G., Williams, C. & Zolla-Pazner, S. ( 1998; ). 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 72, 9384–9391.
    [Google Scholar]
  41. O'Connor, D. H., Mothe, B. R., Weinfurter, J. T., Fuenger, S., Rehrauer, W. M., Jing, P., Rudersdorf, R. R., Liebl, M. E., Krebs, K. & other authors ( 2003; ). Major histocompatibility complex class I alleles associated with slow simian immunodeficiency virus disease progression bind epitopes recognized by dominant acute-phase cytotoxic-T-lymphocyte responses. J Virol 77, 9029–9040.[CrossRef]
    [Google Scholar]
  42. Ohgimoto, S., Shioda, T., Mori, K., Nakayama, E. E., Hu, H. & Nagai, Y. ( 1998; ). Location-specific, unequal contribution of the N glycans in simian immunodeficiency virus gp120 to viral infectivity and removal of multiple glycans without disturbing infectivity. J Virol 72, 8365–8370.
    [Google Scholar]
  43. Pinschewer, D. D., Perez, M., Jeetendra, E., Bachi, T., Horvath, E., Hengartner, H., Whitt, M. A., de la Torre, J. C. & Zinkernagel, R. M. ( 2004; ). Kinetics of protective antibodies are determined by the viral surface antigen. J Clin Invest 114, 988–993.[CrossRef]
    [Google Scholar]
  44. Puffer, B. A., Pohlmann, S., Edinger, A. L., Carlin, D., Sanchez, M. D., Reitter, J., Watry, D. D., Fox, H. S., Desrosiers, R. C. & Doms, R. W. ( 2002; ). CD4 independence of simian immunodeficiency virus Envs is associated with macrophage tropism, neutralization sensitivity, and attenuated pathogenicity. J Virol 76, 2595–2605.[CrossRef]
    [Google Scholar]
  45. Regier, D. A. & Desrosiers, R. C. ( 1990; ). The complete nucleotide sequence of a pathogenic molecular clone of simian immunodeficiency virus. AIDS Res Hum Retroviruses 6, 1221–1231.
    [Google Scholar]
  46. Reimann, K. A., Parker, R. A., Seaman, M. S., Beaudry, K., Beddall, M., Peterson, L., Williams, K. C., Veazey, R. S., Montefiori, D. C. & other authors ( 2005; ). Pathogenicity of simian-human immunodeficiency virus SHIV-89.6P and SIVmac is attenuated in cynomolgus macaques and associated with early T-lymphocyte responses. J Virol 79, 8878–8885.[CrossRef]
    [Google Scholar]
  47. Reitter, J. N., Means, R. E. & Desrosiers, R. C. ( 1998; ). A role for carbohydrates in immune evasion in AIDS. Nat Med 4, 679–684.[CrossRef]
    [Google Scholar]
  48. Schmitz, J. E., Johnson, R. P., McClure, H. M., Manson, K. H., Wyand, M. S., Kuroda, M. J., Lifton, M. A., Khunkhun, R. S., McEvers, K. J. & other authors ( 2005; ). Effect of CD8+ lymphocyte depletion on virus containment after simian immunodeficiency virus SIVmac251 challenge of live attenuated SIVmac239Δ3-vaccinated rhesus macaques. J Virol 79, 8131–8141.[CrossRef]
    [Google Scholar]
  49. Silvera, P., Flanagan, B., Kent, K., Rud, E., Powell, C., Corcoran, T., Bruck, C., Thiriart, C., Haigwood, N. L. & Stott, E. J. ( 1994; ). Fine analysis of humoral antibody response to envelope glycoprotein of SIV in infected and vaccinated macaques. AIDS Res Hum Retroviruses 10, 1295–1304.[CrossRef]
    [Google Scholar]
  50. Smith, D. G. & McDonough, J. ( 2005; ). Mitochondrial DNA variation in Chinese and Indian rhesus macaques (Macaca mulatta). Am J Primatol 65, 1–25.[CrossRef]
    [Google Scholar]
  51. Wei, X., Decker, J. M., Wang, S., Hui, H., Kappes, J. C., Wu, X., Salazar-Gonzalez, J. F., Salazar, M. G., Kilby, J. M. & other authors ( 2003; ). Antibody neutralization and escape by HIV-1. Nature 422, 307–312.[CrossRef]
    [Google Scholar]
  52. Wyatt, R. & Sodroski, J. ( 1998; ). The HIV-1 envelope glycoproteins: fusogens, antigens, and immunogens. Science 280, 1884–1888.[CrossRef]
    [Google Scholar]
  53. 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]
    [Google Scholar]
  54. York, J. & Nunberg, J. H. ( 2004; ). 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.[CrossRef]
    [Google Scholar]
  55. Yu, D., Shioda, T., Kato, A., Hasan, M. K., Sakai, Y. & Nagai, Y. ( 1997; ). Sendai virus-based expression of HIV-1 gp120: reinforcement by the V(−) version. Genes Cells 2, 457–466.[CrossRef]
    [Google Scholar]
  56. Zhang, M., Gaschen, B., Blay, W., Foley, B., Haigwood, N., Kuiken, C. & Korber, B. ( 2004; ). Tracking global patterns of N-linked glycosylation site variation in highly variable viral glycoproteins: HIV, SIV, and HCV envelopes and influenza hemagglutinin. Glycobiology 14, 1229–1246.[CrossRef]
    [Google Scholar]
  57. Zolla-Pazner, S. ( 2004; ). Identifying epitopes of HIV-1 that induce protective antibodies. Nat Rev Immunol 4, 199–210.[CrossRef]
    [Google Scholar]
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