1887

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Volume 80, Issue 5

A highly pathogenic simian/human immunodeficiency virus with genetic changes in cynomolgus monkey Free

Abstract

A highly pathogenic simian/human immunodeficiency virus (SHIV), designated C2/1, was obtained by serum passages in cynomolgus monkeys of p-SHIV, an SHIV strain that contains the env gene of pathogenic human immunodeficiency virus type 1 89.6. CD4 lymphocyte depletion was induced within 1 week of the SHIV-C2/1 infection in peripheral blood as well as in various lymphoid organs in all the animals tested, with symptoms of diarrhoea and no increase in body weight, followed by intense viraemia. Serum antibody against Env protein was detected from 4 weeks after the virus infection, while the anti-Gag antibody response was absent in the SHIV-C2/1-infected animals. In contrast, both anti-Gag and anti-Env antibody responses were present in animals infected with p-SHIV or the non-pathogenic SHIV-MN. Sequencing of the env gene of isolates of SHIV-C strains showed conserved amino acid changes in the Env C2 and V3 regions that included changes to negatively charged amino acids, in the cytoplasmic region of gp41 that included a 42 amino acid deletion, and in the Nef protein. The pathogenic SHIV-C2/1-monkey model suggests that virus-specific pathogenicity in SHIV infection may be associated with the absence of anti-Gag antibody responses in animals and may be caused by genetic changes during serum passage .

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© Journal of General Virology 1999
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1999-05-01
2024-04-25
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References

  1. Binley J. M., Klasse P. J., Cao Y., Jones I., Markowitz M., Ho D. D., Moore J. P. 1997; Differential regulation of the antibody responses to Gag and Env proteins of human immunodeficiency virus type 1. Journal of Virology 71:2799–2809
     [Google Scholar]
  2. Clark S. J., Saag M. S., Decker W. D., Campbell-Hill S., Robertson J. L., Veldkamp P. J., Kappes J. C., Hahn B. H., Shaw G. M. 1991; High titers of cytopathic virus in plasma of patients with symptomatic primary HIV-1 infection. New England Journal of Medicine 324:954–960
     [Google Scholar]
  3. Esteban J. I., Shih J. W.-K., Tai C.-C., Bodner A. J., Kay J. W. D., Alter A. J. 1985; Importance of western blot analysis in predicting infectivity of anti-HTLV-III/LAV positive blood. Lancet ii:1083–1086
     [Google Scholar]
  4. Henrard D. R., Phillips J. F., Muenz L. R., Blattner W. A., Wiesner D., Eyster M. E., Goedert J. J. 1995; Natural history of HIV-1 cell-free viremia. Journal of the American Medical Association 274:554–558
     [Google Scholar]
  5. Ho D. D., Moudgil T., Alam M. 1989; Quantitation of human immunodeficiency virus type 1 in the blood of infected persons. New England Journal of Medicine 321:1621–1625
     [Google Scholar]
  6. Honda M., Yamamoto S., Cheng M., Yasukawa K., Suzuki H., Saito T., Osugi Y., Tokunaga T., Kishimoto T. 1992; Human soluble IL-6 receptor: its detection and enhanced release by HIV infection. Journal of Immunology 148:2175–2180
     [Google Scholar]
  7. Honda M., Matsuo K., Nakasone T., Okamoto Y., Yoshizaki H., Kitamura K., Sugiura W., Watanabe K., Fukushima Y., Haga S., Katsura Y., Tasaka H., Komuro K., Yamada T., Asano T., Yamazaki A., Yamazaki S. 1995; Protective immune responses induced by secretion of a chimeric soluble protein from a recombinant Mycobacterium bovis bacillus Calmette–Guérin vector candidate vaccine for human immunodeficiency virus type 1 in small animals. Proceedings of the National Academy of Sciences, USA 92:10693–10697
     [Google Scholar]
  8. Joag S. V., Li Z., Foresman L., Stephens E. B., Zhao L. J., Adany I., Pinson D. M., McClure H. M., Narayan O. 1996; Chimeric simian/human immunodeficiency virus that causes progressive loss of CD4+ T cells and AIDS in pig-tailed macaques. Journal of Virology 70:3189–3197
     [Google Scholar]
  9. Karlsson G. B., Halloran M., Li J., Park I. W., Gomila R., Reimann K. A., Axthelm M. K., Iliff S. A., Letvin N. L., Sodroski J. 1997; Characterization of molecularly cloned simian-human immunodeficiency viruses causing rapid CD4+ lymphocyte depletion in rhesus monkeys. Journal of Virology 71:4218–4225
     [Google Scholar]
  10. Lehner T., Wang Y., Cranage M., Bergmeier L. A., Mitchell E., Tao-Hall G., Dennis M., Cook N., Brookes R., Klavinskis L., Jones I., Doyle C., Ward R. 1996; Protective mucosal immunity elicited by targeted iliac lymph node immunization with a subunit SIV envelope and core vaccine in macaques. Nature Medicine 2:767–775
     [Google Scholar]
  11. Li J., Lord C. I., Haseltine W., Letvin N. L., Sodroski J. 1992; Infection of cynomolgus monkeys with a chimeric HIV-1/SIVmac virus that expresses the HIV-1 envelope glycoproteins. Journal of Acquired Immune Deficiency Syndromes 5:639–646
     [Google Scholar]
  12. Li J. T., Halloran M., Lord C. I., Watson A., Ranchalis J., Fung M., Letvin N. L., Sodroski J. G. 1995; Persistent infection of macaques with simian-human immunodeficiency viruses. Journal of Virology 69:7061–7067
     [Google Scholar]
  13. Lu Y., Salvato M. S., Pauza C. D., Li J., Sodroski J., Manson K., Wyand M., Letvin N., Jenkins S., Touzjian N., Chutkowski C., Kushner N., LeFaile M., Payne L. G., Roberts B. 1996a; Utility of SHIV for testing HIV-1 vaccine candidates in macaques. Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology 12:99–106
     [Google Scholar]
  14. Lu Y., Brosio P., Lafaile M., Li J., Collman R. G., Sodroski J., Miller C. J. 1996b; Vaginal transmission of chimeric simian/human immunodeficiency viruses in rhesus macaques. Journal of Virology 70:3045–3050
     [Google Scholar]
  15. Lu Y., Pauza C. D., Lu X., Montefiori D. C., Miller C. J. 1998; Rhesus macaques that become systemically infected with pathogenic SHIV 89.6-PD after intravenous, rectal, or vaginal inoculation and fail to make an antiviral antibody response rapidly develop AIDS. Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology 19:6–18
     [Google Scholar]
  16. Mellors J. W., Kingsley L. A., Rinaldo C. R. Jr, Todd J. A., Hoo B. S., Kokka R. P., Gupta P. 1995; Quantitation of HIV-1 RNA in plasma predicts outcome after seroconversion. Annals of Internal Medicine 122:573–579
     [Google Scholar]
  17. Mellors J. W., Rinaldo C. R. Jr, Gupta P., White R. M., Todd J. A., Kingsley L. A. 1996; Prognosis in HIV-1 infection predicted by the quantity of virus in plasma. Science 272:1167–1170
     [Google Scholar]
  18. Miller C. J., Marthas M., Greenier J., Lu D., Dailey P. J., Lu Y. 1998; In vivo replication capacity rather than in vitro macrophage tropism predicts efficiency of vaginal transmission of simian immunodeficiency virus or simian/human immunodeficiency virus in rhesus macaques. Journal of Virology 72:3248–3258
     [Google Scholar]
  19. Reimann K. A., Li J. T., Voss G., Lekutis C., Tenner-Racz K., Racz P., Lin W., Montefiori D. C., Lee-Parritz D. E., Lu Y., Collman R. G., Sodroski J., Letvin N. L. 1996a; An env gene derived from a primary human immunodeficiency virus type 1 isolate confers high in vivo replicative capacity to a chimeric simian/human immunodeficiency virus in rhesus monkeys. Journal of Virology 70:3198–3206
     [Google Scholar]
  20. Reimann K. A., Li J. T., Veazey R., Halloran M., Park I. W., Karlsson G. B., Sodroski J., Letvin N. L. 1996b; 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. Journal of Virology 70:6922–6928
     [Google Scholar]
  21. 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. Journal of Virology 65:3514–3520
     [Google Scholar]
  22. Steger K. K., Dykhuizen M., Mitchen J. L., Hinds P. W., Preuninger B. L., Wallace M., Thomson J., Montefiori D. C., Lu Y., Pauza C. D. 1998; CD4+-T-cell and CD20+-B-cell changes predict rapid disease progression after simian-human immunodeficiency virus infection in macaques. Journal of Virology 72:1600–1605
     [Google Scholar]
  23. Stephens E. B., Joag S. V., Sheffer D., Liu Z. Q., Zhao L., Mukherjee S., Foresman L., Adany I., Li Z., Pinson D., Narayan O. 1996; Initial characterization of viral sequences from a SHIV-inoculated pig-tailed macaque that developed AIDS. Journal of Medical Primatology 25:175–185
     [Google Scholar]
  24. Stephens E. B., Mukherjee S., Sahni M., Zhuge W., Raghavan R., Singh D. K., Leung K., Atkinson B., Li Z., Joag S. V., Liu Z. Q., Narayan O. 1997; A cell-free stock of simian-human immunodeficiency virus that causes AIDS in pig-tailed macaques has a limited number of amino acid substitutions in both SIVmac and HIV-1 regions of the genome and has altered cytotropism. Virology 231:313–321
     [Google Scholar]
  25. Yamanaka T., Fujimura Y., Ishimoto S., Yoshioka A., Konishi M., Narita N., Mimaya J., Meguro T., Nakasone T., Okamoto Y., Yoshizaki H., Yamada K., Honda M. 1997; Correlation of titer of antibody to principal neutralizing domain of HIVMN strain with disease progression in Japanese hemophiliacs seropositive for HIV type 1. AIDS Research and Human Retroviruses 13:317–326
     [Google Scholar]
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A highly pathogenic simian/human immunodeficiency virus with genetic changes in cynomolgus monkey
J. Gen. Virol. 80, 1231 (1999); https://doi.org/10.1099/0022-1317-80-5-1231
/content/journal/jgv/10.1099/0022-1317-80-5-1231
/content/journal/jgv/10.1099/0022-1317-80-5-1231
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