Rhesus Macaques That Become Systemically Infected With... : JAIDS Journal of Acquired Immune Deficiency Syndromes (original) (raw)

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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

Lu, Yichen*; Pauza, David C.†; Lu, Xusheng‡; Montefiori, David C.§; Miller, Christopher J.‡∥

*Institute for International Vaccine Development, Cambridge, Massachusetts; †Wisconsin Regional Primate Research Center, Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, Wisconsin; ‡Department of Surgery, Duke University Medical Center, Durham, North Carolina; §Virology and Immunology Unit, California Regional Primate Research Center, and_∥_Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, California, U.S.A.

Address correspondence and reprint requests to Yichen Lu, Institute for International Vaccine Development, 61 Moultin Street, Cambridge, MA 02138, U.S.A; email [email protected].

Manuscript received October 21, 1997; accepted April 17, 1998.

Abstract

Summary:

A new simian-human immunodeficiency virus (SHIV) stock (SHIV 89.6-PD), derived from plasma of a rhesus macaque used for in vivo serial passage of virulence-attenuated SHIV 89.6, produces systemic infection after intravenous, intravaginal, or intrarectal inoculation of rhesus macaques. Infection with this virus results in high levels of viral antigen in plasma, a precipitous decline in CD4+ T-cell counts, and a disease syndrome that is characteristic of AIDS. Rapid progression to disease was associated with failure to seroconvert to viral antigens, whereas longer survival was associated with production of antiviral antibodies. In Intravenously inoculated animals, peak antigenemia occurred at 7 days postinjection (PI) and severe CD4+ depletion occurred at 14 days PI. In mucosally infected animals, peak antigenemia occurred at 14 days PI and severe CD4+ depletion was not evident until 21 days PI. The 1-week delay in both viral antigenemia and CD4+ T-cell decline in mucosally infected animals is consistent with the hypothesis that, following vaginal inoculation, virus dissemination proceeds in a stepwise manner from the mucosal surface to the draining lymph nodes and subsequently to the bloodstream. This animal model can be used to test the ability of HIV-1 envelope-based vaccines to prevent infection or disease after challenge by the three major routes of HIV transmission.