AEGiS-11IAC: Acute infection with primary isolates of HIV-1 in chimpanzees.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

Acute infection with primary isolates of HIV-1 in chimpanzees.

Int Conf AIDS 1996 Jul 7-12; 11:12 (abstract no. We.A.383)
Murthy KK, Conley AJ, Schleif W, Cobb EK, Lunceford SM, Galvan A, Rouse SR, Johnson D, Emini E; Southwest Foundation for Biomedical Research, San Antonio, TX. Fax: (210) 670-3330. E-mail: kmurthy@icarus.sfbr.org.

OBJECTIVE: To determine the pathogenesis of primary isolates of HIV-1 in chimpanzees.

METHODS: Two primary isolates of HIV-1 designated as DH12 and 5016, grown in PBMC cultures were intravenously inoculated into chimpanzees (n = 2; for each isolate).

RESULTS: Infection with DH12 isolate was characterized by plasma viremia during the first 3 weeks post infection, transient loss of CD4 cells, and a decreased response to mitogens. Virus could be readily isolated from PBMCs and the presence of proviral DNA was confirmed by PCR analysis. Quantitative RNA PCR analysis of plasma samples demonstrated a peak of viral RNA at 1 week post infection, followed by a decline to undetectable levels in one animal, but persistence in the other. Clinical observations included skin rashes and lymphadenopathy. Infection of lymph node, cells was confirmed by virus isolation (VI), DNA PCR, and in situ hybridization. Seroconversion became evident by 3 weeks based on ELISA assays, and antibody titers ranged from 104 to 5x104. Infection with 5016 isolate resulted in higher levels of viral RNA copies, reaching a peak of 2-4 million copies/ml at 3-4 weeks post infection, and gradually declined to 104 to 4x104 copies/ml by 15 weeks of infection. Virus was readily isolated from PBMCs and infection was confirmed by DNA PCR. Infection of lymph node cells was confirmed by VI, DNA PCR, and in situ hybridization. Seroconversion became evident at 4 weeks, and antibody titers reached a peak by 10-12 weeks. Interestingly, during the acute phase of infection there was a marked, but transient, decrease in absolute numbers of CD4, and NK cells were evident in all infected animals at 2-4 weeks, followed by lymphocytosis characterized by a selective increase in CD8 cells.

CONCLUSION: The early phase of infection with primary isolates in chimpanzees is similar to infection in humans with some important distinctions, including a relatively rapid clearance of genomic RNA in plasma, rapid recovery in CD4 and NK cell numbers, and CD8 cell lymphocytosis.

Keywords: AEGIS, HIV-1, Pan troglodytes, RNA, Viral, Viremia, Polymerase Chain Reaction, Antigens, CD4, Anti-HIV Agents, In Situ Hybridization, Animal, Human, ICA11

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