Mechanisms of Feline Lentivirus Control and Interference

描述(申请人提供)：猫免疫缺陷病毒(FIV)是一种与HIV相似的慢病毒，它通过粘膜和垂直途径攻击T淋巴细胞，导致致命的免疫缺陷，最近在其宿主物种家猫(Felis Home Tica)中出现。相比之下，包括美洲狮(美洲狮)在内的非家养猫科动物的FIV样慢病毒显然在其宿主种群中存在了很长一段时间，导致慢病毒/宿主适应--类似于非洲非人类灵长类宿主中的猴免疫缺陷病毒(SIV)。在初步研究中，我们发现感染美洲狮慢病毒(PLV)的家猫不会经历临床疾病，产生强烈的抗慢病毒免疫反应，并且在没有临床疾病的情况下，对随后的强毒FIV攻击有部分保护作用。在自然感染PLV的美洲狮队列中的其他初步数据表明，净化选择，即依赖于病毒适合性而不是宿主免疫反应的选择，可能是塑造PLV种群进化的额外或次要的生力军。因此，我们将评估新出现的FIV与更古老的PLV在适应和非适应猫科动物宿主中感染期间的免疫反应和病毒进化选择。这些研究将深入了解宿主下调和/或病毒选择强毒和弱毒物种的机制--与艾滋病毒感染和艾滋病的发病机制、适应和控制有关的问题。

DESCRIPTION (provided by applicant):Feline immunodeficiency virus (FIV) is a lentivirus analogous to HIV in that it targets T lymphocytes via mucosal and vertical pathways, causes fatal immunodeficiency, and has emerged relatively recently in its host species, the domestic cat (Felis domestica). In contrast, the FIV-like lentiviruses of non-domestic felids, including the puma (cougar mountain lion, Felis concolor), have apparently been present in their host populations for long periods of time, leading to lentiviral/host adaptation--analogous to simian immunodeficiency virus (SIV) in African non-human primate hosts. In preliminary studies we have found that domestic cats infected with puma lentivirus (PLV) do not experience clinical disease, develop a strong anti-lentiviral immune response, and are partially protected against subsequent challenge with virulent FIV in the absence of clinical disease. Other preliminary data in a cohort of cougars naturally infected with PLV suggests that purifying selection, i.e., selection dependent upon viral fitness rather than host immune response may be an additional or secondary vital force shaping evolution of the PLV population. We will therefore assess both the immune response and the viral evolutionary selection during infections by the newly emergent FIV vs. the more ancient PLV in their adapted and non-adapted feline hosts. These studies will provide insight into the mechanisms whereby the host downregulates and/or the virus selects virulent versus attenuated species--questions pertinent to the pathogenesis, adaptation, and control of HIV infection and AIDS.