EARLY EVENTS IN MUCOSAL SIV 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。 尽管多年来的努力，有效的艾滋病毒疫苗仍然难以捉摸。此外，关于艾滋病毒感染的最早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，这对开发预防或控制感染的新型疫苗或免疫疗法都是至关重要的。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需的免疫反应的了解。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，人们对此知之甚少。拟议中的研究将对在阴道传播和到达肠道(病毒扩增的来源)之间发生的初始事件进行研究，希望开发出可能阻止病毒到达肠道并在宿主体内建立“滩头阵地”的策略。我们还在研究可以区分进展者和非进展者的最早免疫学事件，以确定免疫的早期免疫学相关性。 到目前为止，我们已经对SIV感染动物的细胞进行了分类，发现CD4CCR5T细胞中存在的病毒比其他亚群多得多，这可能是病毒选择性地输送到肠道的一个来源。其他分类和高灵敏度的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程位置。我们还发现在SIV感染猕猴的组织中，B7-H1(PD-1配体)发生了非常早期的变化，这可能调节了宿主对感染的反应。

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.