EARLY EVENTS IN MUCOSAL SIV 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 代表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。 尽管多年的努力，有效的艾滋病毒疫苗仍然难以捉摸。此外，关于HIV感染中最早的病毒学和免疫学事件以及免疫与感染或疾病进展的相关性仍然存在相当大的争议，这两者对于开发用于预防或控制感染的新型疫苗或免疫治疗剂都是至关重要的。 也许设计有效疫苗的最大障碍是缺乏对保护免受感染和/或从受感染宿主清除病毒所必需的免疫应答的理解。最后，早期的细胞和分子事件，特别是在HIV感染患者的粘膜组织中的事件知之甚少。拟议的研究将研究在阴道中传播和到达肠道（病毒扩增的来源）之间发生的初始事件，希望制定可能防止病毒到达肠道并在宿主中建立“滩头阵地”的策略。 我们也在研究最早期的免疫学事件，这些事件可以区分进展者和非进展者，以确定免疫的早期免疫学相关性。 到目前为止，我们已经从SIV感染的动物中分选了细胞，发现CD 4 + CCR 5 + T细胞中存在的病毒比其他亚群多得多，这可能是病毒如何选择性转运到肠道的来源。 其他分选和高灵敏度的RT-PCR实验正在组织中进行，以确定病毒在粘膜传播后如何以及何时到达远处。我们还发现，在SIV感染的猕猴的组织中，B7-H1（PD-1配体）发生了非常早期的变化，这可能调节宿主对感染的反应。

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. Despite years of effort, an effective vaccine for HIV remains elusive. Further, considerable controversy remains with regard to the earliest virologic and immunologic events in HIV infection, and correlates of immunity to infection or disease progression, which are both critical for developing novel vaccines or immunotherapeutics for prevention or control of infection. Perhaps the greatest obstacle to designing an effective vaccine is a lack of understanding of the immune responses necessary for protection from infection and/or clearance of virus from infected hosts. Finally, early cellular and molecular events, particularly in mucosal tissues of HIV infected patients are poorly understood. The proposed studies will the initial events that occur between the transmission in the vagina and reaching the intestine (source of viral amplification) in hopes to develop strategies that may prevent virus reaching the intestine and establishing a "beachhead" in the host. We are also examining the earliest immunologic events that can distinguish progressors from nonprogressors to determine early immunologic correlates of immunity. To date we have sorted cells from SIV infected animals and found that much more virus is present in CD4+CCR5+ T cells than other subsets, which may be a source of how the virus is selectively transported to the intestine. Other sorting and highly sensitive RT-PCR experiments are being performed in tissues to determine how and when virus reaches distant sites after mucosal transmission. We have also found very early changes in B7-H1 (the PD-1 ligand) occur in tissues of SIV infected macaques which may regulate the host response to infection.