SIVAGM DYNAMICS IN AFRICAN GREEN MONKEYS

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来源获得了主要资金， 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。 天然SIV宿主缺乏疾病进展的潜在机制仍然知之甚少。为了检验SIV感染的AGM由于病毒复制发生在长寿命的感染细胞中而避免AIDS的假设，我们用SIVagm感染了六只动物，并用有效的抗逆转录病毒疗法[ART：（PMPA，替诺福韦）和（FTC，恩曲他滨）]治疗它们。所有AGM均显示血浆病毒血症快速衰减，在ART开始后36小时无法检测到。在PBMC和肠道中观察到病毒载量显著降低。ART后病毒血症衰减的数学建模表明生产性感染细胞的半衰期为4至9.5小时，即，比以前报告的艾滋病毒和SIV的速度更快。ART诱导外周CD 4 + T细胞计数轻微但显著增加，但淋巴结和肠道中CD 4 + T细胞水平无显著变化。同样，ART没有显著改变细胞增殖、活化和凋亡的水平，这些水平在慢性SIVagm感染的AGM中已经很低。总的来说，这些结果表明，在SIVagm感染的AGM中，大部分病毒复制是由短寿命细胞维持的;因此，SIVmac感染猕猴和SIVagm感染AGM之间的疾病结果差异不太可能是由于两种病毒之间体内细胞病变的内在差异。 一项对黑白眉猴的类似研究证实了我们的结果。

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. The mechanisms underlying the lack of disease progression in natural SIV hosts are still poorly understood. To test the hypothesis that SIV-infected AGMs avoid AIDS due to virus replication occurring in long-lived infected cells, we infected six animals with SIVagm and treated them with potent antiretroviral therapy [ART: (PMPA, tenofovir) and (FTC, emtricitabine)]. All AGMs showed a rapid decay of plasma viremia that became undetectable 36 hours after ART initiation. Significant decrease of viral load was observed in PBMCs and intestine. Mathematical modeling of viremia decay post-ART indicates a half-life of productively infected cells ranging from 4 to 9.5 h, i.e., faster than previously reported for HIV and SIV. ART induced a slight but significant increase in peripheral CD4+ T-cell counts but no significant changes in CD4+ T-cell levels in LNs and intestine. Similarly, ART did not significantly change the levels of cell proliferation, activation and apoptosis, already low in chronically SIVagm-infected AGMs. Collectively, these results indicate that, in SIVagm-infected AGMs, the bulk of virus replication is sustained by short-lived cells; therefore, differences in disease outcome between SIVmac infection of macaques and SIVagm infection of AGMs are unlikely due to intrinsic differences of the in vivo cytopathicity between the two viruses. A similar study in Sooty mangabey confirmed our results.