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.The mucosal infectivity of the challenge virus SHIV SF162 P4 was determined in pig-tailed macaques. Twelve pig-tailed macaques were inoculated intrarectally with this virus stock at 1,800 or 360 TCID50 (6 animals at each dose). Plasma viremia was measured by real time RNA PCR and indicated that eleven of the twelve inoculated macaques were infected. One macaque inoculated with 360 TCID50 was not infected or below the level of detection until the last time point of blood collection. All eleven infected macaques showed peak viremia at around two weeks post-infection. Seven animals showed a slow decline on viral load after that time; four continued to show persistent high plasma viral load. At the same time points, CD4+ subset analysis was performed for all macaques. Nine of the eleven infected macaques had a transient decline of CD4+ T cells by week 2 post-inoculation, around the peak of viral load, but they recovered soon after those time points. On other hand, two infected macaques showed progressive and irreversible CD4+ T cell depletion, with CD4+ T cell levels less than 200/ul at 10-12 weeks after infection. One of these two animals developed AIDS-like diseases and was euthanized approx. 15 months after infection. The macaques that became infected seroconverted after the challenge as indicated by the titers of SIV-specific antibodies as well as HIV-1 envelope gp120 antibodies.Together with a similar study conducted by Dr. Chris Miller of UC Davis, these results indicate that: (1) SHIV SF162 P4 has similar infectivity by intrarectal route of infection in pig-tailed macaques as in rhesus macaques; (2) SHIV SF162 P4 infection in pig-tailed macaques appear to be more robust than that in rhesus monkeys, where none of the eleven intrarectal infected rhesus animals showed persistent viremia and CD4+ T cell depletion.
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