Ezrin, Radixin, and Moesin (ERM) proteins function as pleiotropic regulators of human immunodeficiency virus type 1 infection
Ezrin, Radixin, and Moesin (ERM) proteins function as pleiotropic regulators of human immunodeficiency virus type 1 infection
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DOI：
10.1016/j.virol.2008.01.047
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发表时间：
2008-05-25
期刊：
影响因子：
3.7
通讯作者：
Yamamoto, Naoki
中科院分区：
文献类型：
--
作者：
Kubo, Yoshinao;Yoshii, Hiroaki;Yamamoto, Naoki
Ezrin、radixin和moesin（ERM）蛋白在哺乳动物细胞中提供完整膜蛋白和细胞骨架之间的功能连接，以调节膜蛋白动力学和细胞骨架重排。为了评估ERM蛋白在HIV-1生命周期中的潜在作用，我们研究了在表达HIV-1感染受体的人细胞中抑制ERM功能是否会影响HIV-1包膜（Env）介导的HIV-1载体转导和细胞-细胞融合。ezrin显性负突变体的表达或用siRNA敲低ezrin、radixin或膜突蛋白均匀地降低了具有X4-嗜性Env的HIV-1载体的转导滴度。相反，R5-tropic Env HIV-1载体的转导滴度仅通过radixin敲低而降低：ezrin敲低没有可检测的影响，而膜突蛋白敲低反而增加转导滴度。每种ERM支持物对CD4、CCR5和CXCR4或VSV-Env介导的HIV-1载体转导的细胞表面表达没有可检测的影响。最后，单个ERM mRNA的敲除均匀地降低了由X4或R5嗜性Env和HIV-1感染受体介导的细胞-细胞融合的效率。这些结果表明：（i）ERM蛋白作为X4-嗜性HIV-1感染的正调节因子发挥作用，（ii）膜突蛋白在膜融合后的早期步骤还作为R5-嗜性HIV-1病毒感染的负调节因子发挥作用，以及（iii）受体蛋白动力学在R5-和X4-嗜性HIV-1感染中受到不同的调节。(c)2008年爱思唯尔公司All rights reserved.
Ezrin, radixin, and moesin (ERM) proteins supply functional linkage between integral membrane proteins and cytoskeleton in mammalian cells to regulate membrane protein dynamisms and cytoskeleton rearrangement. To assess potential role of the ERM proteins in HIV-1 lifecycle, we examined if suppression of ERM function in human cells expressing HIV-1 infection receptors influences HIV-1 envelope (Env)-mediated HIV-1-vector transduction and cell-cell fusion. Expression of an ezrin dominant negative mutant or knockdown of ezrin, radixin, or moesin with siRNA uniformly decreased transduction titers of HIV-1 vectors having X4-tropic Env. In contrast, transduction titers of R5-tropic Env HIV-1 vectors were decreased only by radixin knockdown: ezrin knockdown had no detectable effects and moesin knockdown rather increased transduction titer. Each of the ERM suppressions had no detectable effects on cell surface expression of CD4, CCR5, and CXCR4 or VSV-Env-mediated HIV-1 vector transductions. Finally, the individual knockdown of ERM mRNAs uniformly decreased efficiency of cell-cell fusion mediated by X4- or R5-tropic Env and HIV-1 infection receptors. These results suggest that (i) the ERM proteins function as positive regulators of infection by X4-tropic HIV-1, (ii) moesin additionally functions as a negative regulator of R5-tropic HIV-1 virus infection at the early step(s) after the membrane fusion, and (iii) receptor protein dynamisms are regulated differently in R5- and X4-tropic HIV-1 infections. (c) 2008 Elsevier Inc. All rights reserved.