SIVSMM SUBTYPES INDUCE IMMUNOLOGIC AND VIROLOGIC CHANGES IN SOOTY MANGABEYS

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。 SIVsmm自然感染煤烟芒果(Sms)，是人类和猕猴分别感染HIV-2和SIVmac的病原源病毒。在以前的研究中，我们研究了自然感染SIV的SIVsmm的多样性，并鉴定了9个不同的系统发育亚型，它们的遗传距离与已报道的不同HIV-1 M亚型的相似。 在这里，我们报告，在耶尔克斯中心安置的SMS群体中，至少有四个SIVsmm亚型共同循环，绝大多数动物感染SIVsmm亚型1、2或3型，导致偶尔出现重组形式。虽然这些动物表现出典型的非致病感染过程，但我们观察到不同的SIVsmm亚型实际上与特定的免疫学特征有关。值得注意的是，虽然亚型1、2和3型与非常良性的感染过程和正常的CD4+T细胞计数的保存有关，但感染亚型5型的四分之三的SM显示CD4+T细胞显著耗尽。感染亚型5的SM中的病毒复制与感染其他SIVsmm亚型的SM中的病毒复制相似，这一事实表明与亚型5相关的CD4+T细胞耗竭不太可能简单地反映出病毒介导的对CD4+T细胞的更高水平的直接杀伤。综上所述，对自然SM宿主中SIVsmm感染的亚型特异性特征的系统分析确定了SIVsmm感染的亚型特异性差异。

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. SIVsmm naturally infects sooty mangabeys (SMs) and is the source virus of pathogenic infections with HIV-2 and SIVmac of humans and macaques, respectively. In previous studies we characterized SIVsmm diversity in naturally SIV-infected SMs and identified 9 different phylogenetic subtypes whose genetic distances are similar to those reported for the different HIV-1 group M subtypes. Here we report that, within the colony of SMs housed at the Yerkes Center, at least four SIVsmm subtypes co-circulate, with the vast majority of animals infected with SIVsmm subtype 1, 2, or 3, resulting in the emergence of occasional recombinant forms. While these animals show a typically non-pathogenic course of infection, we have observed that different SIVsmm subtypes are in fact associated with specific immunologic features. Notably, while subtypes 1, 2, and 3 are associated with a very benign course of infection and preservation of normal CD4+ T-cell counts, three out of four SMs infected with subtype 5 show a significant depletion of CD4+ T-cells. The fact that virus replication in SMs infected with subtype 5 is similar to that of SMs infected with other SIVsmm subtypes suggest that the subtype 5-associated CD4+ T-cell depletion is unlikely to simply reflect higher levels of virus-mediated direct killing of CD4+ T-cells. Taken together, this systematic analysis of the subtype-specific features of SIVsmm infection in natural SM hosts identifies subtype-specific differences in the pathogenicity of SIVsmm infection.