Foot-and-mouth disease virus 3C protease induces fragmentation of the Golgi compartment and blocks intra-Golgi transport.
Foot-and-mouth disease virus 3C protease induces fragmentation of the Golgi compartment and blocks intra-Golgi transport.
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DOI：
10.1128/jvi.01355-13
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发表时间：
2013-11
影响因子：
5.4
通讯作者：
Wileman T
中科院分区：
文献类型：
--
作者：
Zhou Z;Mogensen MM;Powell PP;Curry S;Wileman T
小核糖核酸病毒感染可引起高尔基体断裂并在分泌途径中施加阻断，其减少质膜处的主要组织相容性抗原的表达并减缓促炎细胞因子的分泌。在这项研究中，我们表明，高尔基体碎片和块分泌诱导表达口蹄疫病毒（FMDV）3Cpro，这需要蛋白酶活性的3Cpro。3Cpro引起早期、中期和晚期高尔基体区室的碎裂，但对早期高尔基体区室的影响最显著，表现为ERGIC 53和membrane的重新分布。高尔基体片段分散在细胞质中，并能够接受模型膜蛋白出口的内质网（ER）。然而，高尔基体片段不能将蛋白质转移到质膜，表明高尔基体内转运受阻。高尔基体断裂与微管组织的损失是一致的，这是由于中心体抑制微管再生长造成的。微管再生长的抑制也需要3Cpro蛋白酶活性。3Cpro诱导的微管组织的丧失导致高尔基体碎裂，但微管组织的丧失并不阻断高尔基体内的运输。这是可能的，内高尔基体运输的块是由单独的行动3Cpro，可能通过降解蛋白质内高尔基体运输所需的。
Picornavirus infection can cause Golgi fragmentation and impose a block in the secretory pathway which reduces expression of major histocompatibility antigens at the plasma membrane and slows secretion of proinflammatory cytokines. In this study, we show that Golgi fragmentation and a block in secretion are induced by expression of foot-and-mouth disease virus (FMDV) 3Cpro and that this requires the protease activity of 3Cpro. 3Cpro caused fragmentation of early, medial, and late Golgi compartments, but the most marked effect was on early Golgi compartments, indicated by redistribution of ERGIC53 and membrin. Golgi fragments were dispersed in the cytoplasm and were able to receive a model membrane protein exported from the endoplasmic reticulum (ER). Golgi fragments were, however, unable to transfer the protein to the plasma membrane, indicating a block in intra-Golgi transport. Golgi fragmentation was coincident with a loss of microtubule organization resulting from an inhibition of microtubule regrowth from the centrosome. Inhibition of microtubule regrowth also required 3Cpro protease activity. The loss of microtubule organization induced by 3Cpro caused Golgi fragmentation, but loss of microtubule organization does not block intra-Golgi transport. It is likely that the block of intra-Golgi transport is imposed by separate actions of 3Cpro, possibly through degradation of proteins required for intra-Golgi transport.