1887

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Volume 76, Issue 6

Repeated exposure of rhesus macaques to low doses of simian immunodeficiency virus (SIV) did not protect them against the consequences of a high-dose SIV challenge Free

Abstract

As part of an titration study of the macaque simian immunodeficiency virus (SIVmac) strain 251/spl, macaques were inoculated intravenously with various dilutions of this infectious SIVmac. Seven animals received dilutions from 10 to 10 of SIVmac. Two monkeys infected with the 10 dilution of SIVmac exhibited a productive infection as indicated by seroconversion, detection of genomic RNA and proviral DNA and positive virus isolation. These animals showed a cytotoxic T cell (CTL) response against different SIVmac proteins without any measurable T cell proliferation. The five macaques receiving higher virus dilutions did not seroconvert and were negative for both viral RNA and for infectious virus, although proviral DNA was detected in their peripheral blood mononuclear cells. In contrast to the animals receiving the 10 virus dilution, these five silently infected monkeys developed an SIV-specific proliferative T cell response but SIV-specific CTL could not be observed. The SIV-specific T cell proliferation of the silently infected animals could be boosted by a second low-dose exposure with a 10 or 10 dilution of SIVmac. The virological status of the animals was not changed following this second virus inoculation. Four months later these macaques were challenged intravenously with 2 ml of a 10 dilution of SIVmac containing 10 monkey ID. After this challenge all SIV-pre-exposed animals and three naive controls became productively infected. In addition, all infected animals developed typical signs of an immunodeficiency within 6 months after infection. These observations indicate that macaques infected silently by a low-dose exposure to infectious virus generated a virus-specific cellular immune response. However, SIV-specific T cell proliferation alone could not protect the monkeys against an intravenous challenge with SIVmac and the subsequent development of AIDS-like symptoms.

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© Journal of General Virology 1995
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1995-06-01
2024-04-25
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References

  1. Baskerville A., Ramsay R. W., Cranage M. P., Cook N., Cook R. W., Dennis M. J., Greenaway P. J., Kitchin P. A., Stott E. J. 1990; Histopathological changes in simian immunodeficiency virus infection. Journal of Pathology 162:67–75
     [Google Scholar]
  2. Clerici M., Shearer G. M. 1993; A TH1-TH2 switch is a critical step in the etiology of HIV infection. Immunology Today 14:107–111
     [Google Scholar]
  3. Clerici M., Giorgi J. V., Chou C.-C., Gudeman V. K., Zack J. A., Gupta P., Ho H. N., Nishanian P. G., Berzofsky J. A., Shearer G. M. 1992; Cell-mediated immune response to human immunodeficiency virus (HIV) type 1 in seronegative homosexual man with recent sexual exposure to HIV-1. Journal of Infectious Diseases 165:1012–1019
     [Google Scholar]
  4. Clerici M., Sison A. V., Berzofsky J. A., Rakusan T. A., Brandt C. D., Ellaurie M., Villa Ml., Colie C., Venzon D. J., Sever J. L., Shearer G. M. 1993; Cellular immune factors associated with mother-to-infant transmission of HIV. AIDS 7:1427–1433
     [Google Scholar]
  5. Clerici M., Levin J. M., Kessler H. A., Harris A., Berzofsky J. A., Shearer G. M. 1994a; HIV-specific T-helper activity in seronegative health care workers exposed to contaminated blood. Journal of the American Medical Association 5:42–46
     [Google Scholar]
  6. Clerici M., Clark E. A., Polacino P., Axberg I., Kuller L. R., Casey N. L., Morton W. R., Shearer G. M., Benveniste R. E. 1994b; T cell proliferation to subinfectious SIV correlates with lack of infection after challenge of macaques. AIDS 8:1391–1395
     [Google Scholar]
  7. Coulibaly C., Stahl-Hennig C., Makoschey B., Petry H., Jurkiewicz E., Fuchs D., Wachter H., Luke W., Hunsmann G. 1995; Passive immunization against SIVmac with purified hyperimmune IgG. In The Proceedings of the VIIIth African Conference on AIDS & Sexually Transmitted Diseases in Africa (in press)
    [Google Scholar]
  8. Cranage M. P., Cook N., Johnstone P., Greenaway P., Kitchin P. A., Stott E. J., Almond N., Baskerville A. 1990; SIV infection of rhesus macaques: in vitro titration of infectivity and development of an experimental vaccine. In Animal Models in AIDS pp 103–114 Edited by Schellekens H. Amsterdam: Elsevier;
     [Google Scholar]
  9. Decker T., Lohmann-Matthes M. L. 1988; A quick and simple method for the quantitation of lactate dehydrogenase release in measurement of cellular cytotoxicity and tumor necrosis factor (TNF) activity. Journal of Immunological Methods 115:61–69
     [Google Scholar]
  10. Desrosiers R. C., Wyand M., Kodama T., Ringler D. J., Arthur L. O., Sehgal P. K., Letvin N. L., King N. W., Daniel M. D. 1989; Vaccine protection against simian immunodeficiency virus infection. Proceedings of the National Academy of Sciences, USA 86:6353–6357
     [Google Scholar]
  11. Dittmer U., Schaffner J., Bodemer W., Petry H., Stahl-Hennig C., Hunsmann G. 1994a; HIV-2-specific immune status of an HIV-2-exposed but uninfected cynomolgus monkey offspring. Viral Immunology 7:47–49
     [Google Scholar]
  12. Dittmer U., Lüke W., Stahl-Hennig C., Coulibaly C., Petry H., Bodemer W., Hunsmann G., Voss G. 1994b; Early helper T cell dysfunction in SIV- but not HIV-2-infected macaques. Journal of Medical Prtmatology 23:21–26
     [Google Scholar]
  13. Eldridge J. H., Staas J. K., Chen D., Marx P. A., Tice T. R., Gilley R. M. 1993; New advances in vaccine delivery systems. Seminars in Hematology 30: Supplement 416–24
     [Google Scholar]
  14. Emini E., Schleif W. A., Nunberg J. H., Conley A. J., Eda Y., Tokiyoshi S., Putney S. D., Matsushita S., Cobb J. C. M., Eichberg J. W., Murthy K. K. 1992; Prevention of HIV-1 infection in chimpanzees by gpl20 V3 domain-specific monoclonal antibody. Nature 355:728–730
     [Google Scholar]
  15. Fendrich C., Lüke W., Stahl-Hennig C., Herchenröder O., Fuchs D., Wachter H., Hunsmann G. 1989; Urinary neopterin concentration in rhesus monkeys after infection with simian immunodeficiency virus (Sivmac251). AIDS 3:305–307
     [Google Scholar]
  16. Fuchs D., Hausen A., Reignegger G., Werner E. R., Dierich M. P., Wachter H. 1988; Neopterin as a marker for activated cell mediated immunity. Immunology Today 9:150–155
     [Google Scholar]
  17. Imagawa D. T., Lee M. H., Wolinsky S. M., Sano K., Morales F., Kwok S., Sninsky J. J., Nishanian P. G., Giorgi J., Fahey J. L., Dudley J., Visscher B. R., Detels R. 1989; Human immunodeficiency virus type 1 infection in homosexual men who remain seronegative for prolonged periods. New England Journal of Medicine 320:1458–1462
     [Google Scholar]
  18. Kent K. A., Kitchin P., Mills K. H. G., Page M., Taffs F., Corcoran T., Silvera P., Flanagan B., Powell C., Rose J., Ling C., Aubertin A. M., Stott E. J. 1994; Passive immunization of cynomolgous macaques with immune sera or pooled neutralizing monoclonal antibodies failed to protect against challenge with SIVmac251. AIDS Research and Human Retroviruses 2:189–194
     [Google Scholar]
  19. Kornfeld H., Riedel N., Viglianti G. A., Hirsch V., Mullins J. I. 1987; Cloning of HTLV-IV and its relation to simian and human immunodeficiency viruses. Nature 326:610–613
     [Google Scholar]
  20. Korzeniewski C., Callewaert D. M. 1983; An enzyme-release assay for natural cytotoxicity. Journal of Immunological Methods 64:313–320
     [Google Scholar]
  21. Letvin N., King N. W. J. 1990; Immunologic and pathologic manifestations of the infection of rhesus monkeys with simian immunodeficiency virus of macaques. AIDS 3:1023–1040
     [Google Scholar]
  22. Lüke W., Stahl-Hennig C., Voss G., Dittmer U., Bodemer W., Makoschey B., Jurkiewicz E., Petry H., Coulibaly C., Hunsmann G. 1994; Immunization with virus-derived gpl30 micelles protects rhesus monkeys against challenge with SIV-mac251/32 grown either on human T cells or prepared directly from the spleen of an SIV-infected rhesus monkey. In Vaccines 94 pp 231–235 Edited by Norrby E. New York: Cold Spring Habor Laboratory;
     [Google Scholar]
  23. Murphey-Corb M., Martin L. N., Davison-Fairburn B., Montelaro R., Miller M., West M., Ohkawa S., Baskin G. B., Zhang J. Y., Putney S., Allison A. C., Eppstein D. 1989; A formalin-inactivated whole SIV vaccine confers protection in macaques. Science 246:1293–1297
     [Google Scholar]
  24. Petry H., Jurkiewicz E., Makoschey B., Stahl-Hennig C., Coulibaly C., Luke W., Dittmer U., Hunsmann G. 1994; Activation of HIV-2ben by superinfection with SIVmac251/32H is correlated with protection against disease in macaques. In Vaccines 94 pp 243–246 Edited by Norrby E. New York: Cold Spring Habor Laboratory;
     [Google Scholar]
  25. Putkonen P., Thorstensson R., Albert J., HlLD K., Norby P., Biberfeld P., Biberfeld G. 1990; Infection of cynomolgus monkeys with HIV-2 protects against pathogenic consequences of a subsequent simian immunodeficiency virus infection. AIDS 4:783–789
     [Google Scholar]
  26. Putkonen P., Thorstensson R., Ghavamzadeh L., Albert J., Hild K., Biberfeld G., Norrby E. 1991; Prevention of HIV-2 and SIVsm infection by passive immunization in cynomolgus monkeys. Nature 352:436–438
     [Google Scholar]
  27. Ranki A., Valle S. L., Krohn M., Antonen J., Allain J.-P., Leuther M., Franchini G., Krohn K. 1987; Long latency precedes overt seroconversion in sexually transmitted human-immunodeficiency-virus infection. Lancet ii:589–593
     [Google Scholar]
  28. Salahuddin S. Z., Markham P. D., Wong-Stahl F., Franchini G., Kalynaraman V. S., Gallo R. C. 1983; Restricted expression of human T cell leukemia-lymphoma virus (HTLV) in transformed human umbilical cord blood lymphocytes. Virology 129:51–64
     [Google Scholar]
  29. Salk J., Bretscher P. A., Salk P. L., Clerici M., Shearer G. M. 1993; A strategy for prophylactic vaccination against HIV. Science 260:1270–1272
     [Google Scholar]
  30. Salvato M. S., Emau P., Malkovsky M., Schultz K. T., Johnson E., Pauza C. D. 1994; Cellular immune responses in rhesus macaques infected rectally with low dose simian immunodeficiency virus. Journal of Medical Primotology 23:125–130
     [Google Scholar]
  31. Stahl-Hennig C., Herchenröder O., Nick S., Evers M., Stille-Siegener M., Jentsch K.-D., Kirchhoff F., Tolle T., Gates-mann T. J., Lüke W., Hunsmann G. 1990a; Experimental infection of macaques with HIV-2ben, a novel HIV-2 isolate. AIDS 4:611–617
     [Google Scholar]
  32. Stahl-Hennig C., Fendrich C., Lüke W., Fuchs D., Reibnegger G., Wachter H., Hunsmann G. 1990b; Infection of macaques with SIV and HIV-2 induces a virus-specific increase of urinary neopterin. In 8th Annual Symposium on Nonhuman Primate Models for AIDS Abstract 70 New Orleans, Lousiana:
     [Google Scholar]
  33. Stahl-Hennig C., Voss G., Nick S., Petry H., Fuchs D., Wachter H., Coulibaly C., Luke W., Hunsmann G. 1992; Immunization with Tween–ether-treated SIV adsorbed onto aluminium hydroxide protects monkeys against experimental SIV infection. Virology 186:588–596
     [Google Scholar]
  34. Vaira D., Francois-Gerard C., Doppagne A., Sondag-Thull D., Rentier B. 1990; Diagnosis by PCR of HIV-1 infection in seronegative individuals at risk. AIDS Research and Human Retroviruses 6:173–174
     [Google Scholar]
  35. Voss G., Nick S., Stahl-Hennig C., Ritter K., Hunsmann G. 1992a; Generation of macaque B lymphoblastoid cell lines with simian Epstein-Barr-like viruses: transformation procedure, characterization of cell lines and occurrence of simian foamy virus. Journal of Virological Methods 39:185–195
     [Google Scholar]
  36. Voss G., Nick S., Stahl-Hennig C., Coulibaly C., Petry H., Luke W., Hunsmann G. 1992b; Potential significance of the cellular immune response against the macaque strain of simian immunodeficiency virus (SIVMAC) in immunized and infected rhesus macaques. Journal of General Virology 73:2273–2281
     [Google Scholar]
  37. Voss G., Nick S., Otteken A., Luke W., Stahl-Hennig C., Hunsmann G. 1992c; Virus-specific cytotoxic T-lymphocytes in HIV-2-infected cynomolgus macaques. AIDS 6:1077–1083
     [Google Scholar]
  38. Voss G., Dittmer U., Nick S., Stahl-Hennig C., Coulibaly C., Petry H., Luke W., Hunsmann G. 1993; Induction of T cell proliferation in rhesus macaques immunized with Tween-ether-treated SIVmac and loss of proliferative activity after virus infection. In Animal Models of HIV Infection pp 86–94 Edited by Racz P. Basel: Karger;
     [Google Scholar]
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Repeated exposure of rhesus macaques to low doses of simian immunodeficiency virus (SIV) did not protect them against the consequences of a high-dose SIV challenge
J. Gen. Virol. 76, 1307 (1995); https://doi.org/10.1099/0022-1317-76-6-1307
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