Considerable research efforts have been directed at the development of an effective vaccine for AIDS, but a cost-effective animal model for HIV-1 is not available for testing the efficacies of these candidate vaccines. Persistent infection of monkeys with SIV recombinant viruses carrying the HIV-1 env gene and portions of the tat and rev genes (SHIV) have recently been reported.
Three specific aims are proposed, the objective of which is to establish SIV infection of monkeys as an animal model for studies related to HIV-1 vaccine development. The env genes of four biologically and serologically distinct HIV-1 isolates will be substituted into the pathogenic SIVmac239 clone, and the ability of these chimeric viruses to infect macaque PBMC in vitro and to establish persistent infection in vivo will be determined. Possible changes in the biologic and serologic properties of the viruses in infected animals over time will be examined and correlate with any changes in their clinical status. Moreover, the antiviral immune responses, particularly the presence of neutralizing or enhancing antibodies in the infected animals will be monitored. This parameter is important in developing this animal model for vaccine evaluation. In addition, the env genes of the HIV-1 strains to be used also contain the genetic determinants of certain in vitro properties of HIV-1 that correlate with its virulence in the host (e.g., cellular host range and cytopathicity). Therefore, these SHIV viruses could potentially provide a system for analyzing, in non-human primates, pathogenic consequences of HIV-1 env and/or other gene expression.
| Harouse, J M; Tan, R C; Gettie, A et al. (1998) Mucosal transmission of pathogenic CXCR4-utilizing SHIVSF33A variants in rhesus macaques. Virology 248:95-107 |
| Levy, J A (1996) The value of primate models for studying human immunodeficiency virus pathogenesis. J Med Primatol 25:163-74 |
