IQGAP1 Negatively Regulates HIV-1 Gag Trafficking and Virion Production.,Cell Reports

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IQGAP1 Negatively Regulates HIV-1 Gag Trafficking and Virion Production.
Cell Reports ( IF 7.5 ) Pub Date : 2020-03-24 , DOI: 10.1016/j.celrep.2020.03.002
Yosef Sabo ₁ , Kenia de Los Santos ₂ , Stephen P Goff ₂

Affiliation

IQGAP1 is a master regulator of many cellular processes, including intracellular vesicle trafficking and endocytosis. We show that depletion of IQGAP1 in a variety of cell types increases the release of HIV-1 infectious virions and that overexpression diminishes virion production, with neither affecting the early stages of infection. IQGAP1 negatively regulates the steady-state levels of HIV-1 Gag at the plasma membrane, the site of assembly. We establish that IQGAP1 interacts with both the nucleocapsid and p6 domains of Gag, and interaction with either domain is sufficient for its regulatory function. Finally, we demonstrate that IQGAP1 regulation is independent of HIV-1 Gag "late-domains" sequences required by the virus to recruit the cellular ESCRT machinery. Thus, we provide evidence that IQGAP1 is a negative regulatory factor inhibiting efficient budding of HIV-1 by reducing Gag accumulation at the plasma membrane.

中文翻译：

IQGAP1 对 HIV-1 Gag 贩运和病毒粒子产生负调控。

IQGAP1 是许多细胞过程的主要调节因子，包括细胞内囊泡运输和内吞作用。我们表明，在多种细胞类型中 IQGAP1 的消耗会增加 HIV-1 感染性病毒粒子的释放，而过度表达会减少病毒粒子的产生，而不会影响感染的早期阶段。IQGAP1 在质膜（组装部位）负调节 HIV-1 Gag 的稳态水平。我们确定 IQGAP1 与 Gag 的核衣壳和 p6 结构域相互作用，并且与任一结构域的相互作用足以实现其调节功能。最后，我们证明 IQGAP1 调节独立于病毒募集细胞 ESCRT 机制所需的 HIV-1 Gag“晚期域”序列。因此，

更新日期：2020-03-26

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