PHENOTYPIC AND GENOTYPIC DETERMINANTS OF SHIV PATHOGENESIS

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。次级项目的主要支助 子项目的主要研究者可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 表示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。 SIV或SHIV感染的非人灵长类动物（NHP）已被用于研究辅助受体的使用对CD 4 + T细胞区室的组成和动力学，疾病诱导和临床综合征的发展机制的影响。由于整个感染过程可以遵循，与频繁访问的组织隔室，感染恒河猴与CCR 5嗜性SHIV进一步允许研究HIV-1辅助受体开关静脉和粘膜接种后，纵向和系统的分析，以确定的时间，解剖部位和包膜糖蛋白和辅助受体偏好的变化的原因。在这里，我们回顾了我们目前的理解辅助受体使用NHP及其对感染的病理生物学特征的影响，并讨论了NHP研究的最新进展，以揭示潜在的选择性压力在体内辅助受体偏好的变化。

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.