IMMUNOPATHOGENESIS OF CLADE C SHIV-1157IPD3N4 IN M NEMESTRINA

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。 我们之前曾报道，在感染SHV病毒后，辫尾猕猴的多个粘膜部位的CD4+T细胞迅速而大量地丢失。感染后2-3周，CD28-CD95+效应记忆细胞和CD28-CCR5+T细胞严重耗竭，这与SHIV1157ipd3N4的R5趋向性一致。在超过感染急性期的三只动物中，两只在GT 48周内表现出持续性血浆病毒血症，其余一只将血浆病毒载量控制在基线水平(102拷贝/毫升)。在感染24周后，两种持续感染病毒的动物都产生了交叉分支中和抗体。然而，两只动物都出现了与猿猴艾滋病一致的临床症状，并被安乐死。在Ruth Ruprecht博士和Charles Wood博士的合作下，我们研究了感染猪尾猕猴的病毒序列的进化，并与感染了带有相同包膜基因的病毒的人和恒河猴进行了比较。初步结果表明，在病毒感染过程中，这三个物种的包膜基因都发生了类似的变化，进一步支持了以猕猴物种作为研究人类艾滋病毒感染的模型。

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. We previously reported the rapid and substantial loss of CD4+ T cells at multiple mucosal sites in pigtailed macaques following SHIV infection. By 2-3 wks post-infection, profound depletion of CD4+CCR5+ T cells cells and CD28-CD95+ effector memory cells were observed, consistent with the R5-tropism of SHIV1157ipd3N4. Two of the three animals that were studied beyond the acute phase of infection showed persistent plasma viremia for gt 48 wks, while the remaining one controlled its plasma viral load at baseline (102 copies p ml). Cross-clade neutralizing antibodies developed in both persistently viremic animals starting at 24 weeks after infection. However, both animals developed clinical signs consistent with simian AIDS and were euthanized. In collaboration with Drs. Ruth Ruprecht and Charles Wood, we studied the evolution of viral sequences in infected pig-tailed macaques as compared to human and rhesus macaques infected with viruses bearing the same envelope gene. Preliminary results indicated that similar changes occurred in the envelope gene during the course of viral infection in all three species, lending further support to the use of macaque species as model to study HIV infection in humans.