TRANSMISSION & PATHOGENESIS OF X4 & R5 SHIVS

该子项目是利用资源的许多研究子项目之一 由NIH/NCRR资助的中心赠款提供。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， 包括其他NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 过渡性中间体与最初的R5病毒相比的适应性劣势被认为是辅助受体转换的障碍之一，解释了X4病毒的晚期出现。使用猿猴模型的人类免疫缺陷病毒1型（HIV-1）辅助受体开关，我们在这项研究中表明，类似的分子进化途径辅助受体开关发生在一个以上的R5猿猴/人类免疫缺陷病毒（SHIV）（SF 162 P3 N）感染的猕猴。在受感染的动物中，多种扩增或转换为CXCR 4的途径共存，过渡中间体在辅助受体使用效率中的适应性影响它们在感染病毒群体中的生长和代表性。双嗜性病毒和X4病毒出现在不同的疾病阶段，但它们的进入效率低于共存的R5病毒株，这可能解释了为什么它们没有胜过R5病毒。在两个受感染的猕猴与辅助受体开关，提供在体内的证据，健身劣势是一个障碍，X4出现和扩展。

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. Fitness disadvantage of the transitional intermediates compared to the initial R5 viruses has been suggested to constitute one of the blockades to coreceptor switching, explaining the late appearance of X4 viruses. Using a simian model for human immunodeficiency virus type 1 (HIV-1) coreceptor switching, we demonstrate in this study that similar molecular evolutionary pathways to coreceptor switch occur in more than one R5 simian/human immunodeficiency virus (SHIV)(SF162P3N)-infected macaque. In infected animals where multiple pathways for expansion or switch to CXCR4 coexist, fitness of the transitional intermediates in coreceptor usage efficiency influences their outgrowth and representation in the infecting virus population. Dualtropic and X4 viruses appear at different disease stages, but they have lower entry efficiency than the coexisting R5 strains, which may explain why they do not outcompete the R5 viruses. Similar observations were made in two infected macaques with coreceptor switch, providing in vivo evidence that fitness disadvantage is an obstacle to X4 emergence and expansion.