SOCS1 is an inducible host factor during HIV-1 infection and regulates the intracellular trafficking and stability of HIV-1 Gag
SOCS1 is an inducible host factor during HIV-1 infection and regulates the intracellular trafficking and stability of HIV-1 Gag
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DOI：
10.1073/pnas.0704831105
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发表时间：
2008-01-08
影响因子：
11.1
通讯作者：
Yamamoto, Naoki
中科院分区：
文献类型：
--
作者：
Ryo, Akihide;Tsurutan, Naomi;Yamamoto, Naoki
人类免疫缺陷病毒1型(HIV-1)利用受感染宿主细胞的大分子机制来产生后代病毒。参与HIV-1复制途径的细胞因子的发现为病毒-宿主细胞相互作用的分子基础提供了进一步的洞察。在此，我们报道了细胞因子信号转导抑制因子1(SOCS1)在HIV-1感染过程中是一个可诱导的宿主因子，并调节HIV-1复制途径的晚期。SOCS1可以直接与HIV-1 P55 Gag多聚蛋白的基质和核衣壳区域结合，增强其稳定性和转运能力，从而通过一种不依赖于干扰素信号的机制高效地生产HIV-1颗粒。SiRNA耗尽SOCS1减少了HIV-1 Gag的靶向运输和组装，导致其作为核周固体聚集体积累，最终受到溶酶体降解。这些结果表明，SOCS1是一个重要的宿主因子，调节HIV-1 Gag的细胞内动态，因此可能成为治疗艾滋病及其相关疾病的新靶点。
Human immunodeficiency virus type 1 (HIV-1) utilizes the macromolecular machinery of the infected host cell to produce progeny virus. The discovery of cellular factors that participate in HIV-1 replication pathways has provided further insight into the molecular basis of virus-host cell interactions. Here, we report that the suppressor of cytokine signaling 1 (SOCS1) is an inducible host factor during HIV-1 infection and regulates the late stages of the HIV-1 replication pathway. SOCS1 can directly bind to the matrix and nucleocapsid regions of the HIV-1 p55 Gag polyprotein and enhance its stability and trafficking, resulting in the efficient production of HIV-1 particles via an IFN signaling-independent mechanism. The depletion of SOCS1 by siRNA reduces both the targeted trafficking and assembly of HIV-1 Gag, resulting in its accumulation as perinuclear solid aggregates that are eventually subjected to lysosomal degradation. These results together indicate that SOCS1 is a crucial host factor that regulates the intracellular dynamism of HIV-1 Gag and could therefore be a potential new therapeutic target for AIDS and its related disorders.