PHENOTYPIC AND GENOTYPIC DETERMINANTS OF SHIV PATHOGENESIS

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 非人类灵长类动物 (NHP) 的 SIV 或 SHIV 感染已用于研究辅助受体的使用对 CD4 T 细胞区室的组成和动态、疾病诱导和临床综合征发展的机制的影响。由于可以跟踪整个感染过程，并且经常进入组织区室，因此用 CCR5 嗜性 SHIV 感染恒河猴进一步可以研究静脉内和粘膜接种后的 HIV-1 辅助受体转换，并通过纵向和系统分析来确定包膜糖蛋白和辅助受体偏好变化的时间、解剖部位和原因。在这里，我们回顾了目前对 NHP 中辅助受体的使用及其对感染病理生物学特征的影响的理解，并讨论了 NHP 研究的最新进展，以揭示体内辅助受体偏好变化的潜在选择压力。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. SIV or SHIV infection of nonhuman primates (NHP) has been used to investigate the impact of coreceptor usage on the composition and dynamics of the CD4+ T cell compartment, mechanisms of disease induction and development of clinical syndrome. As the entire course of infection can be followed, with frequent access to tissue compartments, infection of rhesus macaques with CCR5-tropic SHIVs further allows for study of HIV-1 coreceptor switch after intravenous and mucosal inoculation, with longitudinal and systemic analysis to determine the timing, anatomical sites and cause for the change in envelope glycoprotein and coreceptor preference. Here, we review our current understanding of coreceptor use in NHPs and their impact on the pathobiological characteristics of the infection, and discuss recent advances in NHP studies to uncover the underlying selective pressures for the change in coreceptor preference in vivo.