AEGiS-11IAC: Immunopathogenesis in rhesus macaques infected with SIV/HIV-1 (SHIV) recombinant virus.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

Immunopathogenesis in rhesus macaques infected with SIV/HIV-1 (SHIV) recombinant virus.

Int Conf AIDS 1996 Jul 7-12; 11:14 (abstract no. We.A.401)
Cheng-Mayer C, Luciw PA; Aaron Diamond AIDS Research Center, New York, NY.

OBJECTIVE: To elucidate functions of HIV-1 genes in a non-human primate model, we have constructed infectious recombinant viruses (chimeras) between the pathogenic molecular clone SIVmac239 and molecular clones of HIV-1 that differ in phenotypic properties controlled by the env gene.

METHODS: HIV-1SF33 is a T-cell line-tropic virus which induces syncytia, and HIV-1SF162 is a macrophage-tropic virus which does not induce syncytia. A DNA fragment encoding tat, rev, and env (gp160) of SIVmac239 has been replaced with the counterpart genetic region of HIV-1SF33 and HIV-1SF162 to derive SHIVSF33 and SHIVSF162, respectively.

RESULTS: In the acute infection stage, juvenile rhesus macaques inoculated with SHIVSF33 showed levels of viremia similar to macaques infected with SIVmac239, whereas virus loads were 10-to 100-fold lower in macaques infected with SIVSF162. In the chronic infection stage, macaques infected with SHIVSF33 also exhibited higher virus loads than macaques infected with SHIVSF162. At 80 to 100 weeks, one macaque infected with SHIVSF33 developed signs of simian AIDS (i.e., lymphopenia, dramatically reduced CD4/CD8 ratio, weight loss, diarrhea, and high virus load). Blood collected at 100 weeks from this animal was transfused into two healthy uninfected rhesus macaques. These recipients contained high levels of virus and displayed severe decline in CD4 lymphocytes in peripheral blood in the acute stage of infection; both animals are being monitored for development of simian AIDS. DNA sequence analysis of the transmitted SHIVSF33 reveals multiple changes in the HIV-1 env gene. One or more of these sequence changes may be critical for high virus load and immunodeficiency in SHIV-infected macaques.

CONCLUSIONS: SHIVSF33 establishes persistent infection and causes immunosuppression in rhesus macaques. These findings demonstrate the utility of the SHIV/macaque model for analyzing HIV-1 env gene functions and evaluating HIV-1 env antigen vaccines.

Keywords: AEGIS, SIV, Simian Acquired Immunodeficiency Syndrome, HIV-1, Macaca mulatta, Genes, env, Viral Load, Macaca, CD4-Positive T-Lymphocytes, Animal, Human, genetics, ICA11

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