This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.During the reporting period, we test how well a simian-human immunodeficiency virus (SHIV) is transmitted across different mucosal surfaces. 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 (Song et al., Journal of Virology 2006; 80:8729-38). This virus was inoculated intrarectally, intravaginally, and orally into rhesus monkeys. Recently, we have completed the vaginal titration, and we determined and compared the 50% animal 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.We previously had constructed another clade C SHIV, termed SHIV-2873Ni, and adapted it to rhesus monkeys. We now have isolated the animal-passaged form of this virus, termed SHIV-2873Nip, a virus that was replication competent in rhesus macaque peripheral blood mononuclear cells (PBMC) of all random donors tested. The passaged virus was 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 also saw early signs of disease induced by this virus, including depletion of gut CD4 T lymphocytes, loss of memory T cells in blood, and thrombocytopenia. Future studies will be conducted to determine which SHIV will be preferentially transmitted when animals are mucosally inoculated with a mix of R5 and X4 SHIVs.
Showing the most recent 10 out of 912 publications
