Rho GTPase inhibitorARHGDIB/D4GDI limits HIV-1 replication
Rho GTPase inhibitorARHGDIB/D4GDI limits HIV-1 replication
复制标题
Rho GTP 酶抑制剂 ARHGDIB/D4GDI 限制 HIV-1 复制
DOI：
10.1089/aid.2011.0180
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发表时间：
2011
影响因子：
1.5
通讯作者：
10人中9番目
中科院分区：
文献类型：
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作者：
Watanabe T;Urano E;Koyanagi Y;KomanoJ;10人中9番目
Rho GTP酶能够影响人类免疫缺陷病毒1型（HIV-1）的复制。然而，很少有人知道的调节HIV-1复制的鸟嘌呤核苷酸解离抑制剂（GDIs），三个主要的监管机构之一的Rho GTdR活化周期。从基于T细胞的cDNA文库筛选，ARHGDIB/RhoGDIβ，造血谱系特异性GDI家族蛋白，被鉴定为HIV-1复制的负调节因子。ARHGDIB的上调减弱了HIV-1在多种T细胞系中的复制。结果表明：（1）在稳态条件下，RhoA和Rac 1的显著部分（而非Cdc 42）以GTP结合的活性形式存在，（2）异位ARHGDIB表达降低了F-肌动蛋白含量以及RhoA和Rac 1的活性形式，和（3）通过ARHGDIB的异位表达或抑制HIV-1 Env-1的RhoA信号级联反应，HIV-1感染被减弱。病毒生命周期的早期阶段。这与先前的发现非常一致，即RhoA和Rac 1通过增加受体聚集和病毒-细胞膜融合的效率来促进HIV-1进入。总之，ARHGDIB是HIV-1复制的淋巴特异性内在负调节因子，通过同时抑制RhoA和Rac 1功能发挥作用。
Rho GTPases are able to influence the replication of human immunodeficiency virus type 1 (HIV-1). However, little is known about the regulation of HIV-1 replication by guanine nucleotide dissociation inhibitors (GDIs), one of the three major regulators of the Rho GTPase activation cycle. From a T cell-based cDNA library screening, ARHGDIB/RhoGDIβ, a hematopoietic lineage-specific GDI family protein, was identified as a negative regulator of HIV-1 replication. Up-regulation of ARHGDIB attenuated the replication of HIV-1 in multiple T cell lines. The results showed that (1) a significant portion of RhoA and Rac1, but not Cdc42, exists in the GTP-bound active form under steady-state conditions, (2) ectopic ARHGDIB expression reduced the F-actin content and the active forms of both RhoA and Rac1, and (3) HIV-1 infection was attenuated by either ectopic expression of ARHGDIB or inhibition of the RhoA signal cascade at the HIV-1 Env-dependent early phase of the viral life cycle. This is in good agreement with the previous finding that RhoA and Rac1 promote HIV-1 entry by increasing the efficiency of receptor clustering and virus-cell membrane fusion. In conclusion, the ARHGDIB is a lymphoid-specific intrinsic negative regulator of HIV-1 replication that acts by simultaneously inhibiting RhoA and Rac1 functions.