To elucidate the functions of HIV-1 genes in a non-human primate model, we 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. 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 was replaced with the counterpart genetic region of HIV-1SF33 and HIV-1SF162 to derive SHIVSF33 and SHIVSF162, respectively. Four rhesus macaques were inoculated with each recombinant virus by the intravenous route, and all were shown to be infected by virus isolation and seroconversion. In the acute infection stage, macaques inoculated with SHIVSF33 had levels of viremia similar to macaques infected with SIVMAC239, whereas virus loads were 10- to 100-fold lower in macaques infected with SHIVSF162. Of note is the relatively small amount of virus detected in lymph nodes of shivsf162 infected macaques. In the chronic infection stage, macaques infected with SHIVSF33 showed higher virus loads than macaques infected with SHIVSF162. Virus persists for over one year as demonstrated by polymerase chain reaction for amplification of viral dna in all animals and by virus isolation in some. Antiviral antibodies, including antibodies to the HIV-1 env glycoprotein (gp160), were detected; titers of antiviral antibodies were higher in macaques infected with SHIVSFf33 than with SHIVSF162. Although virus has persisted for over one year after inoculation, these animals have remained healthy with no signs of immunodeficiency. These findings demonstrate the utility of the SHIV/macaque model for analyzing HIV-1 env gene functions and evaluating vaccines based on HIV-1 env antigens.
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