This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. When strains of lentiviruses become available, it is important to determine the infectivity, pathogenicity, and minimal infectious dose of each virus in a nonhuman primate species before it can be used in vaccine trails or therapeutic testing. This project allows lentiviruses to be tested in vivo. Simian-Human Immunodeficiency Virus 89.6p (SHIV 89.6p) is a chimeric virus derived from a parent virus (SHIV 89.6) composed of SIVmac239 expressing HIV env and the associated auxiliary genes. This parent virus was shown to replicate to a high degree in rhesus monkeys in primary infection, but pathogenic consequences of chronic infection were not seen. After two serial in vivo passages by intravenous blood inoculation of rhesus monkeys, the resulting SHIV (SHIV 89.6p) induced CD4 lymphopenia and an AIDS-like disease with wasting and opportunistic infections in these monkeys. SHIV 89.6p has been used widely in nonhuman primate models to test HIV vaccine strategies at a number of institutions. However, in none of these studies was a definitive 50% animal infectious dose ever determined. The current study was done to increase knowledge for the Macaca fascicularis species. Eight adult M. fascicularis of Indonesian origin were inoculated intravenously with dilutions of SHIV 89.6p Mm K542 ranging from 1:1000 through 1:100,000. Blood for T-cell subset evaluation, plasma viral load, and serum antibody concentrations was collected periodically. All animals except for the one inoculated with a 1:100,000 dilution became infected from between one and three weeks post-inoculation. Two of the three inoculated with a 1:1000 dilution experienced depletion of their CD4+ T cells, while this cell population declined in the remaining 1:1000 dilution animal and the 2 1:5000 dilution animals, but was not depleted. All animals remain clinically healthy at sixteen weeks post-inoculation. We anticipate continuing to study the animals through at least 24 weeks post-inoculation.
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