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. We have tested how well a simian-human immunodeficiency virus (SHIV) is transmitted across different mucosal surfaces in rhesus macaques. This virus, termed SHIV-1157ipd3N4, is a unique virus generated by our laboratory;it encodes the envelope gene of an R5 HIV-1 clade C African isolate which was transmitted from a mother to her child. This virus was inoculated intrarectally, intravaginally, and orally into rhesus monkeys. We determined and compared the 50% animal infectious doses and minimal infectious doses for the three different mucosal routes;we noted significant differences among all routes tested;virus transmission was easiest by the rectal route, followed by the intravaginal route and lastly, the oral route. In addition, we have performed an intrarectal titration in rhesus monkeys of Chinese origin, using the identical virus stock. This allows a direct comparison of the relative mucosal transmissibility of the SHIV-1157ipd3N4 in the two sets of monkeys. We previously had constructed another clade C SHIV, termed SHIV-2873Ni, and adapted it to rhesus monkeys. The animal-passaged form of this virus, termed SHIV-2873Nip, remained exclusively R5 tropic and its env gene clustered with clade C viruses in phylogenetic analysis. We have determined that SHIV-2873Nip is mucosally transmissible;rhesus monkeys were infected orally and intrarectally. We have also performed a titration using multiple low-dose of virus. We noticed early signs of disease induced by this virus, including depletion of gut CD4 T lymphocytes, loss of memory T cells in blood, and thrombocytopenia. Studies focused on which SHIV will be preferentially transmitted mucosally are ongoing;animals were mucosally inoculated with a mix of R5 and X4 SHIVs.
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