RESERVOIRS OF SIV IN LONG TERM NONPROGRESSORS IN RHESUS MACAQUES

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 本项目共招募了12只中国恒河猴（Ch Rh），感染了高致病性分子克隆SIVmac 239。我们以前的研究表明，Ch Rh在SIV感染后有两种不同的临床结果：a）AIDS的发展比印度恒河猴慢（平均2年），和B）三分之一是长期非进展者（LTNP），其在急性SIV感染后具有持续检测不到的血浆病毒载量，并存活长达6年。在这项研究中，12只动物中有6只是LTNP，病毒载量低至检测不到（2.2 ~ 3.0）。 3 log 10 SIV RNA拷贝数/ml），其余6例均为SIVmac感染进展者，病毒载量为3.5 ~ 6.3 log 10 SIV RNA拷贝数。 在此期间，对每只动物进行一次切除空肠和结肠活检，如可能，还获得淋巴细胞和肠系膜淋巴结。 肠组织固有层淋巴细胞（LPL）的产量是可变的，这取决于动物的条件。肠道淋巴细胞的免疫表型分析表明，结肠LPL比空肠LPL具有相对更多的静息CD 4 + T细胞。记忆性CCR 5 + CD 4 + T细胞（SIV靶细胞）在LTNP中结肠LPL中保持高于空肠LPL，而这些靶细胞在进展者中几乎完全耗尽。在LTNP的结肠中可检测到前病毒DNA，表明结肠可能是储库。 通过实时PCR定量细胞SIV病毒RNA和前病毒DNA正在进行中。

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.