A role for endoplasmic reticulum exit sites in foot-and-mouth disease virus infection.
A role for endoplasmic reticulum exit sites in foot-and-mouth disease virus infection.
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内质网出口位点的作用，是脚和口疾病病毒感染的作用。
DOI：
10.1099/vir.0.055442-0
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发表时间：
2013-12
期刊：
影响因子：
--
通讯作者：
Jackson T
中科院分区：
文献类型：
--
作者：
Midgley R;Moffat K;Berryman S;Hawes P;Simpson J;Fullen D;Stephens DJ;Burman A;Jackson T
小核糖核酸病毒与细胞膜一起复制其基因组。虽然肠道病毒被认为利用早期分泌途径的膜，但口蹄疫病毒（FMDV）用于复制的膜的来源尚不清楚。通过早期分泌途径的分泌-囊泡交通是由COPII和COPI两种不同的膜外衣复合物的顺序获取介导的，并且需要Sar1、Arf1和Rab蛋白的协调作用。Sar1对于在内质网（ER）出口位点（ERESs）产生COPII囊泡至关重要，而Arf1和Rab1则是COPI囊泡随后的囊泡运输所必需的。在目前的研究中，我们已经提供了证据，证明FMDV需要早期分泌途径的前高尔基体膜来感染。Sar1的小干扰RNA缺失或Sar1a的显性阴性（DN）突变体的表达抑制FMDV感染。相比之下，Sar1a的显性活性突变体允许COPII囊泡形成，但通过稳定COPII外壳抑制分泌途径，导致er -高尔基体中间室（ERGIC）的严重破坏，但没有抑制感染。用brefeldin A或表达Arf1和Rab1a的DN突变体处理细胞，破坏高尔基体并增强FMDV感染。这些结果表明，阻断ERESs早期分泌通路的试剂对FMDV感染有抑制作用，而在ERESs退出后立即阻断ERGIC和高尔基体之前阻断早期分泌通路的试剂更有利于感染。总之，这些观察结果证明了Sar1在FMDV感染中的作用，以及最初的病毒复制发生在ERESs形成的膜上。
Picornaviruses replicate their genomes in association with cellular membranes. While enteroviruses are believed to utilize membranes of the early secretory pathway, the origin of the membranes used by foot-and-mouth disease virus (FMDV) for replication are unknown. Secretory-vesicle traffic through the early secretory pathway is mediated by the sequential acquisition of two distinct membrane coat complexes, COPII and COPI, and requires the coordinated actions of Sar1, Arf1 and Rab proteins. Sar1 is essential for generating COPII vesicles at endoplasmic reticulum (ER) exit sites (ERESs), while Arf1 and Rab1 are required for subsequent vesicle transport by COPI vesicles. In the present study, we have provided evidence that FMDV requires pre-Golgi membranes of the early secretory pathway for infection. Small interfering RNA depletion of Sar1 or expression of a dominant-negative (DN) mutant of Sar1a inhibited FMDV infection. In contrast, a dominant-active mutant of Sar1a, which allowed COPII vesicle formation but inhibited the secretory pathway by stabilizing COPII coats, caused major disruption to the ER–Golgi intermediate compartment (ERGIC) but did not inhibit infection. Treatment of cells with brefeldin A, or expression of DN mutants of Arf1 and Rab1a, disrupted the Golgi and enhanced FMDV infection. These results show that reagents that block the early secretory pathway at ERESs have an inhibitory effect on FMDV infection, while reagents that block the early secretory pathway immediately after ER exit but before the ERGIC and Golgi make infection more favourable. Together, these observations argue for a role for Sar1 in FMDV infection and that initial virus replication takes place on membranes that are formed at ERESs.
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影响因子：
11.8
作者：
Grigoriev, Ilya;Splinter, Daniel;Akhmanova, Anna
通讯作者：
Akhmanova, Anna
影响因子：
4
作者：
Dumaresq-Doiron, Karine;Savard, Marie-France;Lefrancois, Stephane
通讯作者：
Lefrancois, Stephane
影响因子：
30.3
作者：
Coyne CB;Bozym R;Morosky SA;Hanna SL;Mukherjee A;Tudor M;Kim KS;Cherry S
通讯作者：
Cherry S
影响因子：
5.4
作者：
Armer, Hannah;Moffat, Katy;Monaghan, Paul
通讯作者：
Monaghan, Paul
DOI：
10.1083/jcb.200509095
发表时间：
2005-12-19
期刊：
The Journal of cell biology
影响因子：
--
作者：
Bielli A;Haney CJ;Gabreski G;Watkins SC;Bannykh SI;Aridor M
通讯作者：
Aridor M