PHENOTYPIC AND GENOTYPIC DETERMINANTS OF SHIV PATHOGENESIS

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 非人灵长类动物的SIV或SIV感染(NHP)被用来研究辅受体的使用对CD4T细胞的组成和动力学的影响，疾病的诱发机制和临床症状的发展。由于可以跟踪整个感染过程，并经常接触组织间隔，感染CCR5嗜性SHIV的恒河猴进一步允许研究静脉和粘膜接种后HIV-1辅助受体的切换，并进行纵向和系统分析，以确定包膜糖蛋白和辅助受体偏好变化的时间、解剖位置和原因。在这里，我们回顾了目前我们对NHP中辅助受体的使用及其对感染的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改变的潜在选择压力。

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.