IN VIVO EVALUATION OF PRIMATE LENTIVIRUSES

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. When strains of lentiviruses become available, it is important to determine the infectivity, pathogenicity, and minimal infectious dose of each virus in a particular nonhuman primate species before it can be used in vaccine trails or therapeutic testing. This project is designed to allow lentiviruses to be tested in vivo. Simian-Human Immunodeficiency Virus-SF162P4 (SHIV SF162P4) is derived from a molecular clone, SHIV SF162, a chimeric virus that contains the env gene of a CCR-5-using primary isolate of subtype B HIV-1. A macaque-passaged stock, SHIV SF162P3 was found to cause a dramatic loss of intestinal T cells followed by a gradual depletion of peripheral T cells. Lymph node cells and PBMC from a macaque infected with the SHIV SF162P3 virus two weeks after infection were amplified in human PBMC to generate a P4 stock virus and a challenge stock was prepared. The current study was undertaken to measure the infectivity and inductive ability of B- and T-cell immune responses by the intravaginal route so that these SHIVs may serve as challenge viruses in future vaccine studies and microbicide trials in Chinese rhesus macaques utilizing this route of infection.