SIVAGM INFECTION OF PIG-TAILED MACAQUES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 比较感染相同SIV毒株和不同临床结果的不同非人类灵长类宿主，可能会更准确地研究导致对艾滋病产生耐药性的宿主因素。目的：(1)利用SIVagm.sab建立PTMS的致病模型；(2)确定初次感染时肠道中CD4T细胞的耗竭是否对PTMS中SIVagm.sab的毒力有预测作用。 本研究包括6个PTM。接种150只TCID50 SIVagmsab92018。 所有6个PTM在接种后第14天至21天(Pi)血清转换。第10天p27高水平的抗原血症证实了SIVagm.sab的成功感染。血浆病毒载量(VLS)在第8-10pi天达到峰值，所有6只动物的血浆病毒载量水平都在(109-1010拷贝/毫升)之间。然而，VLS在感染的慢性期变化很大。其中一只动物保持很高的血浆VLS(108拷贝/毫升)，并在200pi左右死于艾滋病。一只动物在60pi时建立了一个设定点VL，维持在105-106拷贝/毫升。在4只动物中，在60-140pi之间检测不到VL。在进展为艾滋病的动物中，组织VLS极高。 在最初的SIV感染期间，所有动物在肠道中都经历了类似的戏剧性的CD4+T细胞枯竭，这与急性感染期间病毒的高复制一致。初次感染期间的CD4T细胞丢失不能预测临床病程或慢性期的SIVagm.sab病毒血症。 我们的研究表明，未传代(非适应)的SIVagm.sab株可在PTMS中诱导艾滋病。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患者的一般结局。 一次连续传代的SIVagm.sab增加了PTMS的致病性。因此，我们成功地优化了SIVagm在该物种中的感染，为未来的研究奠定了基础。

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.