INTRARECTAL TITRATION OF SHIV 162P4 STOCK

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。子项目的主要支持 而子项目的主要调查员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 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。 我们以前报道了一个比较研究的体内感染性和致病性的CCR 5-热带SHIVSF 162 P4在恒河猴和猪尾猕猴。结果表明，恒河猴和猪尾猕猴对SHIVSF 162 P4通过粘膜途径感染的易感性相似。然而，SHIV复制显着更强大的猪尾猕猴比恒河猴。由于持续性病毒感染与中和抗体应答的扩大相关，因此在实现本研究的主要目标后，我们继续监测了受感染猪尾猕猴亚组中病毒序列和中和抗体活性的演变。这些动物的PBMC被送到杜兰大学的James罗宾逊博士那里，以分离抗HIV-1的中和单克隆抗体。来自罗宾逊博士的初步数据表明，这些抗体中的一些可能识别针对HIV-1包膜的构象依赖性表位。这些抗体的进一步表征正在进行中。

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 a comparative study of the in vivo infectivity and pathogenicity of a CCR5-tropic SHIVSF162 P4 in rhesus and pig-tailed macaques. Results indicate that both rhesus and pig-tailed macaques are similarly susceptible to SHIVSF162 P4 infection by mucosal routes. However, SHIV replication was significantly more robust in pig-tailed macaques than in rhesus. Since, persistent viral infection has been correlated with broadening of neutralizing antibody responses, we continued to monitor the evolution of viral sequences and neutralizing antibody activities in a subset of infected pig-tailed macaques after the primary goal of this study was achieved. PBMC from some of these animals were sent to Dr. James Robinson at Tulane University to isolate neutralizing monoclonal antibodies against HIV-1. Preliminary data from Dr. Robinson indicate that some of these antibodies may recognize conformation-dependent epitopes against HIV-1 envelope. Further characterization of these antibodies is in progress.