SIVAGM INFECTION OF PIG-TAILED MACAQUES

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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. Comparison of different non-human primates hosts infected with the same SIV strain and different clinical outcomes may allow a more accurate study of the host factors responsible of resistance to AIDS. Aims: (1) To develop a pathogenic model in PTMs by using SIVagm.sab; (2) To determine if CD4 T cell depletion in the intestine during primary infection is predictive for SIVagm.sab virulence in PTMs. Six PTMs were included in this study. They were inoculated with 150 TCID50 SIVagmsab92018. All six PTMs seroconverted between days 14 and 21 post-innoculation (pi). The successful SIVagm.sab infection was confirmed by high levels of p27 antigenemia at day 10 pi. Plasma viral loads (VLs) peaked at day 8-10 pi, with very high levels in all six animals between (109-1010 copies/ml). However, VLs were very variable during the chronic phase of infection. One animal maintained very high plasma VLs (108 copies/ml) and died of AIDS at around day 200 pi. One animal established a set point VL by day 60 pi, that was maintained at 105-106 copies/ml. In four animals VLs became undetectable between days 60-140 pi. Tissue VLs were extremely high in the animal that progressed to AIDS. All the animals experienced a similar dramatic CD4+ T cell depletion in the intestine during the primary SIV infection, in agreement with high viral replication during the acute infection. The CD4 T cell loss during the primary infection was not predictive for the clinical course or SIVagm.sab viremia during the chronic phase. Our study shows that non-passaged (non-adapted) SIVagm.sab strain can induce AIDS in PTMs. A longer follow-up is necessary to determine if AIDS is the general outcome in all PTMs infected with SIVagm. A single serial passage of SIVagm.sab increased pathogenicity in PTMs. We therefore succeded to optimize the SIVagm infection in this species for future studies.