1887

Abstract

Previously, we reported that a new genetically diverse CCR5 (R5) tropic simian/human immunodeficiency virus (SHIV-MK38) adapted to rhesus monkeys became more neutralization resistant to SHIV-infected plasma than did the parental SHIV-KS661 clone. Here, to clarify the significance of the neutralization-resistant phenotype of SHIV in a macaque model, we initially investigated the precise neutralization phenotype of the SHIVs, including SHIV-MK38 molecular clones, using SHIV-MK38-infected plasma, a pooled plasma of human immunodeficiency virus (HIV)-infected individuals, soluble CD4 and anti-HIV-1 neutralizing mAbs, the epitopes of which were known. The results show that SHIV-KS661 had tier 1 neutralization sensitivity, but monkey-adapted R5 tropic SHIV-MK38 acquired neutralization resistance similar to that of tier 2 or 3 as a clone virus. Sequence analysis of the gene suggested that the neutralization-resistant phenotype of SHIV-MK38 was acquired by conformational changes in Env associated with the net charge and potential -linked glycosylation sites. To examine the relationship between neutralization phenotype and stably persistent infection in monkeys, we performed rectal inoculation experiments using a SHIV-MK38 molecular clone. The results showed that one of three rhesus monkeys exhibited durable infection with a plasma viral load of 10 copies ml despite the high antibody responses that occurred in the host. Whilst further improvements are required in the development of a challenge virus, it will be useful to generate a neutralization-resistant R5 tropic molecular clone of the SHIV-89.6 lineage commonly used for vaccine development – a result that can be used to explore the foundation of AIDS pathogenesis.

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2016-05-01
2019-10-23
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References

  1. Boyd D. F. , Peterson D. , Haggarty B. S. , Jordan A. P. , Hogan M. J. , Goo L. , Hoxie J. A. , Overbaugh J. . ( 2015;). Mutations in HIV-1 envelope that enhance entry with the macaque CD4 receptor alter antibody recognition by disrupting quaternary interactions within the trimer. J Virol 89: 894–907 [CrossRef] [PubMed].
    [Google Scholar]
  2. Buchbinder S. P. , Mehrotra D. V. , Duerr A. , Fitzgerald D. W. , Mogg R. , Li D. , Gilbert P. B. , Lama J. R. , Marmor M. , other authors . ( 2008;). Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): a double-blind, randomised, placebo-controlled, test-of-concept trial. Lancet 372: 1881–1893 [CrossRef] [PubMed].
    [Google Scholar]
  3. 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]
  4. Casimiro D. R. , Wang F. , Schleif W. A. , Liang X. , Zhang Z.-Q. , Tobery T. W. , Davies M.-E. , McDermott A. B. , O'Connor D. H. , other authors . ( 2005;). Attenuation of simian immunodeficiency virus SIVmac239 infection by prophylactic immunization with DNA and recombinant adenoviral vaccine vectors expressing Gag. J Virol 79: 15547–15555 [CrossRef] [PubMed].
    [Google Scholar]
  5. DuBridge R. B. , Tang P. , Hsia H. C. , Leong P. M. , Miller J. H. , Calos M. P. . ( 1987;). Analysis of mutation in human cells by using an Epstein-Barr virus shuttle system. Mol Cell Biol 7: 379–387 [CrossRef] [PubMed].
    [Google Scholar]
  6. Eda Y. , Takizawa M. , Murakami T. , Maeda H. , Kimachi K. , Yonemura H. , Koyanagi S. , Shiosaki K. , Higuchi H. , other authors . ( 2006;). Sequential immunization with V3 peptides from primary human immunodeficiency virus type 1 produces cross-neutralizing antibodies against primary isolates with a matching narrow-neutralization sequence motif. J Virol 80: 5552–5562 [CrossRef] [PubMed].
    [Google Scholar]
  7. Etemad-Moghadam B. , Sun Y. , Nicholson E. K. , Fernandes M. , Liou K. , Gomila R. , Lee J. , Sodroski J. . ( 2000;). Envelope glycoprotein determinants of increased fusogenicity in a pathogenic simian-human immunodeficiency virus (SHIV-KB9) passaged in vivo . J Virol 74: 4433–4440 [CrossRef] [PubMed].
    [Google Scholar]
  8. 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]
  9. Francica J. R. , Sheng Z. , Zhang Z. , Nishimura Y. , Shingai M. , Ramesh A. , Keele B. F. , Schmidt S. D. , Flynn B. J. , other authors . ( 2015;). Analysis of immunoglobulin trascripts and hypermutation following SHIVAD8 infection and protein-plus-adjuvant immunization. Nat Commun 6: 6565 [CrossRef].
    [Google Scholar]
  10. Fukazawa Y. , Miyake A. , Ibuki K. , Inaba K. , Saito N. , Motohara M. , Horiuchi R. , Himeno A. , Matsuda K. . & other authors ( 2008;). Small intestine CD4+ T cells are profoundly depleted during acute simian-human immunodeficiency virus infection, regardless of viral pathogenicity. J Virol 82: 6039–6044 [CrossRef] [PubMed].
    [Google Scholar]
  11. Gardner M. R. , Kattenhorn L. M. , Kondur H. R. , von Schaewen M. , Dorfman T. , Chiang J. J. , Haworth K. G. , Decker J. M. , Alpert M. D. , other authors . ( 2015;). AAV-expressed eCD4-Ig provides durable protection from multiple SHIV challenges. Nature 519: 87–91 [CrossRef] [PubMed].
    [Google Scholar]
  12. Gautam R. , Nishimura Y. , Lee W. R. , Donau O. , Buckler-White A. , Shingai M. , Sadjadpour R. , Schmidt S. D. , LaBranche C. C. , other authors . ( 2012;). Pathogenicity and mucosal transmissibility of the R5-tropic simian/human immunodeficiency virus SHIVAD8 in rhesus macaques: implications for use in vaccine studies. J Virol 86: 8516–8526 [CrossRef] [PubMed].
    [Google Scholar]
  13. Hsu M. , Harouse J. M. , Gettie A. , Buckner C. , Blanchard J. , Cheng-Mayer C. . ( 2003;). Increased mucosal transmission but not enhanced pathogenicity of the CCR5-tropic, simian AIDS-inducing simian/human immunodeficiency virus SHIV(SF162P3) maps to envelope gp120. J Virol 77: 989–998 [CrossRef] [PubMed].
    [Google Scholar]
  14. Inaba K. , Fukazawa Y. , Matsuda K. , Himeno A. , Matsuyama M. , Ibuki K. , Miura Y. , Koyanagi Y. , Nakajima A. , other authors . ( 2010;). Small intestine CD4+ cell reduction and enteropathy in simian/human immunodeficiency virus KS661-infected rhesus macaques in the presence of low viral load. J Gen Virol 91: 773–781 [CrossRef] [PubMed].
    [Google Scholar]
  15. Javaherian K. , Langlois A. J. , Schmidt S. , Kaufmann M. , Cates N. , Langedijk J. P. , Meloen R. H. , Desrosiers R. C. , Burns D. P. , Bolognesi D. P. . ( 1992;). The principal neutralization determinant of simian immunodeficiency virus differs from that of human immunodeficiency virus type 1. Proc Natl Acad Sci U S A 89: 1418–1422 [CrossRef] [PubMed].
    [Google Scholar]
  16. Kawamura M. , Ishizaki T. , Ishimoto A. , Shioda T. , Kitamura T. , Adachi A. . ( 1994;). Growth ability of human immunodeficiency virus type 1 auxiliary gene mutants in primary blood macrophage cultures. J Gen Virol 75: 2427–2431 [CrossRef] [PubMed].
    [Google Scholar]
  17. Kwong P. D. , Mascola J. R. , Nabel G. J. . ( 2013;). Broadly neutralizing antibodies and the search for an HIV-1 vaccine: the end of the beginning. Nat Rev Immunol 13: 693–701 [CrossRef] [PubMed].
    [Google Scholar]
  18. Letvin N. L. , Mascola J. R. , Sun Y. , Gorgone D. A. , Buzby A. P. , Xu L. , Yang Z.-Y. , Chakrabarti B. , Rao S. S. . & other authors ( 2006;). Preserved CD4+ central memory T cells and survival in vaccinated SIV-challenged monkeys. Science 312: 1530–1533 [CrossRef] [PubMed].
    [Google Scholar]
  19. Matsuda K. , Inaba K. , Fukazawa Y. , Matsuyama M. , Ibuki K. , Horiike M. , Saito N. , Hayami M. , Igarashi T. , Miura T. . ( 2010;). In vivo analysis of a new R5 tropic SHIV generated from the highly pathogenic SHIV-KS661, a derivative of SHIV-89.6. Virology 399: 134–143 [CrossRef] [PubMed].
    [Google Scholar]
  20. Mehandru S. . ( 2007;). The gastrointestinal tract in HIV-1 infection: questions, answers, and more questions!. The PRN Notebook 12 http://www.prn.org/index.php/progression/article/hiv_1_gastrointestinal_galt_267.
    [Google Scholar]
  21. Miyake A. , Ibuki K. , Enose Y. , Suzuki H. , Horiuchi R. , Motohara M. , Saito N. , Nakasone T. , Honda M. , other authors . ( 2006;). Rapid dissemination of a pathogenic simian/human immunodeficiency virus to systemic organs and active replication in lymphoid tissues following intrarectal infection. J Gen Virol 87: 1311–1320 [CrossRef] [PubMed].
    [Google Scholar]
  22. Moore J. P. , Cao Y. , Qing L. , Sattentau Q. J. , Pyati J. , Koduri R. , Robinson J. , Barbas C. F. . , III, Burton, D. R. & Ho, D. D. ( 1995;). Primary isolates of human immunodeficiency virus type 1 are relatively resistant to neutralization by monoclonal antibodies to gp120, and their neutralization is not predicted by studies with monomeric gp120. J Virol 69: 101–109 [PubMed].
    [Google Scholar]
  23. Naganawa S. , Yokoyama M. , Shiino T. , Suzuki T. , Ishigatsubo Y. , Ueda A. , Shirai A. , Takeno M. , Hayakawa S. , other authors . ( 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]
  24. Nishimura Y. , Shingai M. , Willey R. , Sadjadpour R. , Lee W. R. , Brown C. R. , Brenchley J. M. , Buckler-White A. , Petros R. , other authors . ( 2010;). Generation of the pathogenic R5-tropic simian/human immunodeficiency virus SHIVAD8 by serial passaging in rhesus macaques. J Virol 84: 4769–4781 [CrossRef] [PubMed].
    [Google Scholar]
  25. O'Brien W. A. , Sumner-Smith M. , Mao S.-H. , Sadeghi S. , Zhao J.-Q. , Chen I. S. . ( 1996;). Anti-human immunodeficiency virus type 1 activity of an oligocationic compound mediated via gp120 V3 interactions. J Virol 70: 2825–2831 [PubMed].
    [Google Scholar]
  26. O'Connell R. J. , Kim J. H. , Corey L. , Michael N. L. . ( 2012;). Human immunodeficiency virus vaccine trials. Cold Spring Harb Perspect Med 2: a007351 [PubMed].[CrossRef]
    [Google Scholar]
  27. O'Doherty U. , Swiggard W. J. , Malim M. H. . ( 2000;). Human immunodeficiency virus type 1 spinoculation enhances infection through virus binding. J Virol 74: 10074–10080 [CrossRef] [PubMed].
    [Google Scholar]
  28. Otsuki H. , Yoneda M. , Igarashi T. , Miura T. . ( 2014;). Generation of a monkey-tropic human immunodeficiency virus type 1 carrying env from a CCR5-tropic subtype C clinical isolate. Virology 460-461: 1–10 [CrossRef] [PubMed].
    [Google Scholar]
  29. Pitcher C. J. , Hagen S. I. , Walker J. M. , Lum R. , Mitchell B. L. , Maino V. C. , Axthelm M. K. , Picker L. J. . ( 2002;). Development and homeostasis of T cell memory in rhesus macaque. J Immunol 168: 29–43 [CrossRef] [PubMed].
    [Google Scholar]
  30. 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]
  31. Purtscher M. , Trkola A. , Gruber G. , Buchacher A. , Predl R. , Steindl F. , Tauer C. , Berger R. , Barrett N. , other authors . ( 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]
  32. Rasheed M. , Bettadapura R. , Bajaj C. . ( 2015;). Computational refinement and validation protocol for proteins with large variable regions applied to model HIV Env spike in CD4 and 17b bound state. Structure 23: 1138–1149 [CrossRef] [PubMed].
    [Google Scholar]
  33. Reimann K. A. , Li J. T. , Veazey R. , Halloran M. , Park I.-W. , Karlsson G. B. , Sodroski J. , Letvin N. L. . ( 1996;). A chimeric simian/human immunodeficiency virus expressing a primary patient human immunodeficiency virus type 1 isolate env causes an AIDS-like disease after in vivo passage in rhesus monkeys. J Virol 70: 6922–6928 [PubMed].
    [Google Scholar]
  34. 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] [PubMed].
    [Google Scholar]
  35. Repits J. , Sterjovski J. , Badia-Martinez D. , Mild M. , Gray L. , Churchill M. J. , Purcell D. F. , Karlsson A. , Albert J. , other authors . ( 2008;). Primary HIV-1 R5 isolates from end-stage disease display enhanced viral fitness in parallel with increased gp120 net charge. Virology 379: 125–134 [CrossRef] [PubMed].
    [Google Scholar]
  36. Sadjadpour R. , Theodore T. S. , Igarashi T. , Donau O. K. , Plishka R. J. , Buckler-White A. , Martin M. A. . ( 2004;). Induction of disease by a molecularly cloned highly pathogenic simian immunodeficiency virus/human immunodeficiency virus chimera is multigenic. J Virol 78: 5513–5519 [CrossRef] [PubMed].
    [Google Scholar]
  37. Seaman M. S. , Janes H. , Hawkins N. , Grandpre L. E. , Devoy C. , Giri A. , Coffey R. T. , Harris L. , Wood B. , other authors . ( 2010;). Tiered categorization of a diverse panel of HIV-1 Env pseudoviruses for assessment of neutralizing antibodies. J Virol 84: 1439–1452 [CrossRef] [PubMed].
    [Google Scholar]
  38. Shibata R. , Kawamura M. , Sakai H. , Hayami M. , Ishimoto A. , Adachi A. . ( 1991;). Generation of a chimeric human and simian immunodeficiency virus infectious to monkey peripheral blood mononuclear cells. J Virol 65: 3514–3520 [PubMed].
    [Google Scholar]
  39. Shimizu Y. , Okoba M. , Yamazaki N. , Goto Y. , Miura T. , Hayami M. , Hoshino H. , Haga T. . ( 2006;). Construction and in vitro characterization of a chimeric simian and human immunodeficiency virus with the RANTES gene. Microbes Infect 8: 105–113 [CrossRef] [PubMed].
    [Google Scholar]
  40. Shingai M. , Donau O. K. , Schmidt S. D. , Gautam R. , Plishka R. J. , Buckler-White A. , Sadjadpour R. , Lee W. R. , LaBranche C. C. , other authors . ( 2012;). Most rhesus macaques infected with the CCR5-tropic SHIVAD8 generate cross-reactive antibodies that neutralize multiple HIV-1 strains. Proc Natl Acad Sci U S A 109: 19769–19774 [CrossRef] [PubMed].
    [Google Scholar]
  41. Shingai M. , Nishimura Y. , Klein F. , Mouquet H. , Donau O. K. , Plishka R. , Buckler-White A. , Seaman M. , Piatak M. Jr. , other authors . ( 2013;). Antibody-mediated immunotherapy of macaques chronically infected with SHIV suppresses viraemia. Nature 503: 277–280 [PubMed].
    [Google Scholar]
  42. Shinohara K. , Sakai K. , Ando S. , Ami Y. , Yoshino N. , Takahashi E. , Someya K. , Suzaki Y. , Nakasone T. , other authors . ( 1999;). A highly pathogenic simian/human immunodeficiency virus with genetic changes in cynomolgus monkey. J Gen Virol 80: 1231–1240 [CrossRef] [PubMed].
    [Google Scholar]
  43. Shioda T. , Oka S. , Ida S. , Nokihara K. , Toriyoshi H. , Mori S. , Takebe Y. , Kimura S. , Shimada K. , other authors . ( 1994;). A naturally occurring single basic amino acid substitution in the V3 region of the human immunodeficiency virus type 1 env protein alters the cellular host range and antigenic structure of the virus. J Virol 68: 7689–7696 [PubMed].
    [Google Scholar]
  44. Shiver J. W. , Fu T.-M. , Chen L. , Casimiro D. R. , Davies M.-E. , Evans R. K. , Zhang Z.-Q. , Simon A. J. , Trigona W. L. , other authors . ( 2002;). Replication-incompetent adenoviral vaccine vector elicits effective anti-immunodeficiency-virus immunity. Nature 415: 331–335 [CrossRef] [PubMed].
    [Google Scholar]
  45. Stiegler G. , Kunert R. , Purtscher M. , Wolbank S. , Voglauer R. , Steindl F. , Katinger H. . ( 2001;). A potent cross-clade neutralizing human monoclonal antibody against a novel epitope on gp41 of human immunodeficiency virus type 1. AIDS Res Hum Retroviruses 17: 1757–1765 [CrossRef] [PubMed].
    [Google Scholar]
  46. Veazey R. S. , DeMaria M. , Chalifoux L. V. , Shvetz D. E. , Pauley D. R. , Knight H. L. , Rosenzweig M. , Johnson R. P. , Desrosiers R. C. , Lackner A. A. . ( 1998;). Gastrointestinal tract as a major site of CD4+ T cell depletion and viral replication in SIV infection. Science 280: 427–431 [CrossRef] [PubMed].
    [Google Scholar]
  47. Wang X. , Rasmussen T. , Pahar B. , Poonia B. , Alvarez X. , Lackner A. A. , Veazey R. S. . ( 2007;). Massive infection and loss of CD4+ T cells occurs in the intestinal tract of neonatal rhesus macaques in acute SIV infection. Blood 109: 1174–1181 [CrossRef] [PubMed].
    [Google Scholar]
  48. 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]
  49. 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] [PubMed].
    [Google Scholar]
  50. Yuste E. , Sanford H. B. , Carmody J. , Bixby J. , Little S. , Zwick M. B. , Greenough T. , Burton D. R. , Richman D. D. , other authors . ( 2006;). Simian immunodeficiency virus engrafted with human immunodeficiency virus type 1 (HIV-1)-specific epitopes: replication, neutralization, and survey of HIV-1-positive plasma. J Virol 80: 3030–3041 [CrossRef] [PubMed].
    [Google Scholar]
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