VIRAL CYTOPATHICITY IN CD4-LOW SIV PASSAGED MANGABEYS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 在人类感染艾滋病毒和猕猴感染猴免疫缺陷病毒(SIV)的情况下，CD4+T细胞耗尽与疾病进展加速之间的联系已经得到很好的证实。然而，SIV在其自然灵长类宿主中的感染导致了接近正常水平的CD4+T细胞，尽管其血浆病毒载量相似。在Yerkes殖民地的SIV+芒果鼠的血浆转移后，两只芒果鸟的CD4+T细胞水平下降到血液中的低于100个细胞/ul，在淋巴结中也可以观察到这一点。在过去的8年里，这些水平一直保持在18到100个细胞/微升的血液中。艾滋病的存在决定了SIV+曼加比的CD4+T细胞水平，这在Yerkes群体中是不常见的(在筛查的105只SIV+曼加比中，只有4个是CD4低)。这些实验的目的是描述观察到的CD4耗尽背后的机制，以及评估这些曼加比在CD4含量较低的情况下进行免疫反应的能力。 为了进行这项研究，另外三只曼加比感染了来自低CD4细胞的血浆病毒，这三只曼加比的CD4水平在感染后21天下降到低于100个CD4细胞/uL血液。我们最近测试了现在5只CD4-low SIV+芒格比对流感疫苗的反应能力。我们给他们接种了两次疫苗，并将血浆送到疾控中心进行分析，以量化流感特异性抗体的水平。通过这种方式，我们将能够确定即使在它们的CD4+T细胞水平较低的情况下，曼加比是否能够引发有效的免疫反应。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The association between CD4+ T-cell depletion and an accelerated rate of disease progression is well established for HIV infection in humans and simian immunodeficiency virus (SIV) infection in macaques. However, SIV infection in its natural primate host (i.e. sooty mangabeys) results in near normal levels of CD4+ T-cells despite similar plasma viral loads. Following transfer of plasma from an SIV+ mangabey in the Yerkes colony, two mangabeys exhibited a decline in CD4+ T cell levels to below 100 cells/ul of blood which is also be observed in lymph nodes. These levels have remained between 18 and 100 cells/ul of blood for the past 8 years. The presence of AIDS defining CD4+ T-cell levels in SIV+ mangabeys is an uncommon occurrence within the Yerkes colony (only four of the 105 SIV+ mangabeys screened are CD4-low). The goal of these experiments was to characterize the mechanisms behind the observation of CD4 depletion as well as assess the ability of these mangabeys to mount immune responses in a CD4-low mileu. To undertake this study, three additional mangabeys were infected with plasma virus from a CD4-low mangabey and the CD4 levels in these three mangabeys declined to below 100 CD4 cells/ul of blood by 21 days post-infection. We recently tested the ability of the now 5 CD4-low SIV+ mangabeys to respond to an influenza vaccination. We vaccinated them twice and sent the plasma to the CDC for analysis to quantify the levels of influenza specific antibodies. In this way we will be able to determine if mangabeys are able to elicit effective immune responses even when their CD4+ T cell levels are low.