SIVSMM SUBTYPES INDUCE IMMUNOLOGIC AND VIROLOGIC CHANGES IN SOOTY MANGABEYS

SIVSMM 亚型引起乌白眉猴的免疫学和病毒学变化

• 批准号: 7716285
• 负责人: CRISTIAN APETREI
• 金额: $ 6.42万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-21 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7716285
• 关键词: Animals; Benign; Biological Preservation; CD4 Positive T Lymphocytes; Cell Count; Cercocebus atys; Classification; Computer Retrieval of Information on Scientific Projects Database; Funding; Genetic; Grant; HIV-1; HIV-2; Housing; Human; Immunologics; Infection; Institution; Macaca; Mediating; Pathogenicity; Phylogenetic Analysis; Recombinants; Reporting; Research; Research Personnel; Resources; Source; T-Cell Depletion; United States National Institutes of Health; Virus; Virus Replication; killings

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.

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。 SIVsmm天然感染白眉猴（SM），并且分别是人类和猕猴的HIV-2和SIVmac的致病性感染的源病毒。在以前的研究中，我们的特点SIVsmm多样性在自然SIV感染的SM，并确定了9个不同的系统发育亚型，其遗传距离是相似的，为不同的HIV-1 M组亚型的报告。 在这里，我们报告说，在殖民地的SM在耶基斯中心，至少有四个SIVsmm亚型共循环，与绝大多数的动物感染SIVsmm亚型1，2，或3，导致偶尔出现的重组形式。虽然这些动物表现出典型的非致病性感染过程，但我们观察到不同的SIVsmm亚型实际上与特定的免疫学特征相关。值得注意的是，虽然亚型1、2和3与非常良性的感染过程和正常CD 4 + T细胞计数的保存相关，但感染亚型5的四分之三的SM显示出CD 4 + T细胞的显著耗竭。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，这一事实表明亚型5相关的CD 4 + T细胞耗竭不太可能简单地反映更高水平的病毒介导的CD 4 + T细胞直接杀伤。两者合计，这种系统的分析亚型特异性特征的SIVsmm感染在自然SM主机确定亚型特异性差异的致病性SIVsmm感染。