Enteroviruses harness the cellular endocytic machinery to remodel the host cell cholesterol landscape for effective viral replication.
Enteroviruses harness the cellular endocytic machinery to remodel the host cell cholesterol landscape for effective viral replication.
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DOI：
10.1016/j.chom.2013.08.002
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发表时间：
2013-09-11
影响因子：
30.3
通讯作者：
Altan-Bonnet N
中科院分区：
文献类型：
--
作者：
Ilnytska O;Santiana M;Hsu NY;Du WL;Chen YH;Viktorova EG;Belov G;Brinker A;Storch J;Moore C;Dixon JL;Altan-Bonnet N
胆固醇是细胞膜的关键组分，调节膜基蛋白质/脂质复合物的组装和功能。许多RNA病毒，包括肠道病毒，重塑宿主细胞膜以产生具有独特脂质蓝图的细胞器，它们在其上组装复制复合物并合成病毒RNA。在这里，我们发现网格蛋白介导的内吞作用（CME）是利用肠道病毒运输胆固醇从质膜（PM）和细胞外介质的复制细胞器，然后胆固醇调节病毒多蛋白加工，促进基因组合成。当CME被破坏时，细胞胆固醇库反而储存在脂滴中;胆固醇不能被运输到复制细胞器;复制被抑制。相比之下，在胆固醇升高的细胞中，例如缺乏窖蛋白的细胞或尼曼匹克病患者的细胞，复制会受到刺激。我们的研究结果表明胆固醇是肠道病毒复制的关键决定因素，并概述了肠道病毒生命周期和宿主细胞胆固醇稳态中内吞机制的作用。
Cholesterol is a critical component of cellular membranes, regulating assembly and function of membrane-based protein/lipid complexes. Many RNA viruses, including enteroviruses, remodel host membranes to generate organelles with unique lipid blueprints on which they assemble replication complexes and synthesize viral RNA. Here we find that clathrin-mediated endocytosis (CME) is harnessed by enteroviruses to traffic cholesterol from the plasma membrane (PM) and extracellular medium to replication organelles where cholesterol then regulates viral polyprotein processing and facilitates genome synthesis. When CME is disrupted, cellular cholesterol pools are instead stored in lipid droplets; cholesterol cannot be trafficked to replication organelles; and replication is inhibited. In contrast, replication is stimulated in cholesterol-elevated cells like those lacking caveolins or those from Niemann-Pick disease patients. Our findings indicate cholesterol as a critical determinant for enteroviral replication and outline roles for the endocytic machinery in both the enteroviral lifecycle and host cell cholesterol homeostasis.
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影响因子：
56.9
作者：
BROWN, MS;GOLDSTEIN, JL
通讯作者：
GOLDSTEIN, JL
影响因子：
64.5
作者：
ANDINO, R;RIECKHOF, GE;BALTIMORE, D
通讯作者：
BALTIMORE, D
影响因子：
5.4
作者：
BARTON, DJ;FLANEGAN, JB
通讯作者：
FLANEGAN, JB
DOI：
10.1073/pnas.0913828107
发表时间：
2010-02-16
影响因子：
11.1
作者：
Bryleva, Elena Y.;Rogers, Maximillian A.;Chang, Ta-Yuan
通讯作者：
Chang, Ta-Yuan
影响因子：
3.7
作者：
Cornell, CT;Semler, BL
通讯作者：
Semler, BL