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. The mucosal infectivity of the challenge virus SHIV SF162 P4 was determined in pig-tailed macaques. This virus is derived from a molecular clone SHIV SF162, which contains the env gene of a CCR-5-using primary isolate of subtype B HIV-1. A macaque-passaged stock SHIV SF162 P3, was established in Dr. Cecilia Cheng-Mayer's laboratory and was found to caused a dramatic loss of CD4+ intestinal T cells followed by a gradual depletion in peripheral CD4+ T cells (Harouse et al., Science 284:816, 1999). Lymph node cells and PBMC from a macaque infected with the SHIV SF162 P3 virus 2 weeks after infection were amplified in human PBMC in Dr. Cheng-Mayer's laboratory to generate a P4 stock virus. A challenge stock was prepared by Advanced BioScience Laboratories, Inc., through a contract by Dr. Nancy Miller of the Division of AIDS and was made available to the Washington National Primate Research Center for in vivo titration and vaccine studies. The in vitro infectivity of the SHIV SF162 P4 stock is 3.6x103 TCID50/ml on human PBMC. By intrarectal inoculation, 5/6 animals were infected at an inoculum of 1 ml of the stock at 1:10 dilution. The animal with the highest plasma viral load (J04009) had peripheral blood CD4+ T-cell counts below 250/ml at 8 weeks after inoculation. These results confirm the mucosal infectivity of SHIV SF162 P4 in pig-tailed macaques and are in agreement with results of similar infectivity studies in rhesus macaques done by Dr. C. Miller (pers. comm.). Determination of the mucosal infectivity and pathogenicity of SHIV162P4 challenge stock will allow us to use this as the challenge virus for planned macaque studies.
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