SIVAGM INFECTION OF PIG-TAILED 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来源获得了主要资金， 因此可在其他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。 比较不同的非人灵长类宿主感染相同的SIV毒株和不同的临床结果，可能会更准确地研究宿主对艾滋病的耐药性。目的：（1）通过使用SIVagm.sab建立PTM的致病模型;（2）确定原发感染期间肠道中的CD 4 T细胞耗竭是否可预测PTM中的SIVagm.sab毒力。 本研究纳入了6例PTM。它们接种150 TCID 50 SIVagmsab 92018。 所有6种PTM在接种后（pi）第14天和第21天之间发生血清转化。在感染后第10天，通过高水平的p27抗原血症证实了成功的SIVagm.sab感染。血浆病毒载量（VL）在感染后第8-10天达到峰值，所有6只动物的水平均非常高（109-1010拷贝/ml）。然而，VL在感染的慢性阶段非常可变。一只动物维持非常高的血浆VL（108拷贝/ml），并在感染后约200天死于AIDS。一只动物在感染后第60天建立了设定点VL，其维持在105-106拷贝/ml。在四只动物中，VL在第60-140天pi之间变得不可检测。在进展为AIDS的动物中，组织VL极高。 所有动物在原发性SIV感染期间在肠道中经历了类似的戏剧性CD 4 + T细胞耗竭，与急性感染期间的高病毒复制一致。原发感染期间的CD 4 T细胞损失不能预测慢性期的临床病程或SIVagm.sab病毒血症。 我们的研究表明，未传代（非适应）的SIVagm.sab株可以在PTM中诱导AIDS。有必要进行更长时间的随访，以确定艾滋病是否是所有感染SIVagm的PTM的一般结局。 SIVagm.sab的单次连续传代增加了PTM的致病性。因此，我们成功地优化了SIVagm感染在这个物种的未来研究。

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.