Investigating the Role of Innate Immune Factors in Restricting HIV Spread in Macrophages

 描述(申请人提供)：HIV-1蛋白VPR在所有已知的慢病毒中高度保守，然而缺乏VPR的HIV突变体能够在大多数细胞培养中复制 几乎没有瑕疵的模特。维持进化压力的对比表明，在单核细胞来源的巨噬细胞的培养中，VPR-VPR及其在体外的相对不适当还没有完全解释清楚。我们早期的发现空突变体显示病毒粒子的产生和环境蛋白的表达受到限制。此外，C-型凝集素在巨噬细胞中表达，已知与Env亚单位结合。我们的初步数据表明，这种限制依赖于甘露糖受体gp120。我们建议的研究旨在确定Env和病毒粒子是如何被靶向的，并确认导致我们观察到的缺陷的限制因素的身份。该项目的成功完成将提供对先天免疫和病毒逃避机制的洞察。

 DESCRIPTION (provided by applicant): The HIV--‐1 protein Vpr is highly conserved across all known lentiviruses, yet HIV mutants lacking vpr are capable of replicating in most cell culture models with little or no defect. The contrast between the evolutionary pressure to maintain indicate that in cultures of monocyte--‐derived macrophages a vpr--‐ vpr and its relative inconsequence in vitro has not been fully explained. Our earlier findings null mutant displays restricted virion production and Env expression. Additionally C--‐ type lectin expressed in macrophages that is known to bind the Env subunit our preliminary data suggest this restriction is dependent on mannose receptor, a gp120. Our proposed studies aim to determine how Env and virions are targeted and to confirm the identity of the restriction factor responsible for the defects we have observed. Successful completion of the project will provide insight into innate immunity and viral mechanisms of evasion.