RESERVOIRS OF SIV IN LONG TERM NONPROGRESSORS IN RHESUS MACAQUES

这个子项目是众多研究子项目之一

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. Total of 12 Chinese-origin rhesus macaques (Ch Rh) were recruited in this project that were infected with highly pathogenic molecular clone SIVmac239. Our previous studies showed that Ch Rh had two distinct clinical outcomes after SIV infection: a) development of AIDS is slower (average 2 years) than Indian rhesus macaques, and b) one-third were long term nonprogressors (LTNPs) which had persistant undetectable plasma viral loads after acute SIV infection and survive for up to 6 years. In this study, six of the 12 animals were LTNPs with low to undetectable viral loads ( 2.2 ~ 3 log10 SIV RNA copies/ml) in plasma for the time range of more than 2.5 years to 7 years, the other 6 were SIVmac-infected progressors with the viral loads from 3.5 ~ 6.3 log10 SIV RNA copies. Excissoacl Jejunum and colon biopsies were performed once per animal during this period of time and lymphocytes mensenteric lymph nodes were also obtained when possible. The yield of lamina propria lymphocytes (LPL) cells from gut tissue was variable depending on the animal's condition. Immunophenotyping of gut lymphocytes showed that colon LPL had relatively more resting CD4+ T cells remaining than in jejunum LPL. Memory CCR5+ CD4+ T cells (SIV target cells) remained higher in colon LPL than in jejunum LPL in LTNPs, while these target cells were almost completely depleted in progressors. Proviral DNA in colon of LTNPs was detectable indicating that colon is possibly a reservoir. Quantification of cellular SIV viral RNA and proviral DNA by real-time PCR is underway.