Regulation of Cofilin in HIV-1 Infection of Human CD4 T Cells

项目总结： HIV-1感染CD4T细胞，导致T细胞耗尽和免疫缺陷。分子 早期病毒与T细胞之间的相互作用对病毒是至关重要的 感染和发病机制。我们的初步研究已经确定Cofilin是 病毒针对的早期信号分子，以建立潜伏感染 CD4T细胞。我们已经证明HIV-1利用病毒包膜/CXCR4 激活cofilin信号以克服静息时皮质肌动蛋白的限制 CD4T细胞。这一分子事件对于病毒在静止T细胞中的核迁移是必要的 细胞。我们的长期目标是研究病毒与宿主相互作用的分子细节 导致信号异常和粘连蛋白激活。这项建议的具体目的是 研究病毒被膜gp120与其趋化因子辅助受体之间的相互作用， CXCR4，导致粘附素激活。我们将确定gp120上的信号域， 以及绘制相关的信号通路。这项拟议的研究具有重要意义 因为这些信息将有助于识别被 病毒，以促进感染。这些机制与病毒的发病机制高度相关。 在CD4T细胞中。拟议中的研究结果也可能确定新的治疗方法 目标是抑制病毒感染。

Project Summary: HIV-1 infects CD4 T cells and causes T cell depletion and immunodeficiency. Molecular interactions between the virus and T cells that occur at the early time are critical for viral infection and pathogenesis. Our preliminary studies have identified cofilin as one of the early signaling molecules targeted by the virus in order to establish latent infection of CD4 T cells. We have demonstrated that HIV-1 utilizes the viral envelope/CXCR4 signaling to activate cofilin in order to overcome the cortical actin restriction in resting CD4 T cells. This molecular event is necessary for viral nuclear migration in resting T cells. Our long-term goal is to study the molecular details of viral-host interaction that lead to aberrant signaling and cofilin activation. The specific aims of this proposal are to study the interactions between the viral envelope, gp120, and its chemokine coreceptor, CXCR4, that lead to cofilin activation. We will identify the signaling domains on gp120, as well as map the signaling pathways involved. This proposed research is significant because the information will help to identify specific cellular mechanisms hijacked by the virus to facilitate infection. These mechanisms are highly relevant to viral pathogenesis in CD4 T cells. Results from the proposed study may also identify novel therapeutic targets to inhibit viral infection.