Foot-and-Mouth Disease Virus, but Not Bovine Enterovirus, Targets the Host Cell Cytoskeleton via the Nonstructural Protein 3Cpro
Foot-and-Mouth Disease Virus, but Not Bovine Enterovirus, Targets the Host Cell Cytoskeleton via the Nonstructural Protein 3Cpro
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DOI：
10.1128/jvi.00907-08
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发表时间：
2008-11-01
影响因子：
5.4
通讯作者：
Monaghan, Paul
中科院分区：
文献类型：
--
作者：
Armer, Hannah;Moffat, Katy;Monaghan, Paul
口蹄疫病毒（Foot-and-mouth disease virus，FMDV）是小核糖核酸病毒科（Picornaviridae）的成员，是偶蹄动物的病原体，并且引起具有重大经济意义的疾病。小核糖核酸病毒感染的细胞表现出细胞形态的变化和细胞质膜的重排，这是病毒复制的结果。我们在这里显示，通过共聚焦免疫荧光和电子显微镜，口蹄疫病毒感染的细胞的形态学的变化涉及感染过程中的微管和中间丝成分的分布的变化。尽管中心体在感染的细胞中持续存在，但微管与微管组织中心（MTOC）区域的连接丢失。MTOC中γ-微管蛋白而非围中心蛋白的标记丢失表明靶向于γ-微管蛋白（或相关蛋白），而非MTOC结构的完全破坏。通过未感染细胞中单个病毒非结构蛋白及其前体的表达来确定负责的FMDV蛋白的身份。我们报告说，唯一的病毒非结构蛋白能够再现的损失，γ-微管蛋白从MTOC和微管系统的完整性的损失是口蹄疫病毒3Cpro。相比之下，用另一种小核糖核酸病毒（牛肠道病毒）感染细胞并不影响γ-微管蛋白的分布，微管网络相对不受影响。
Foot-and-mouth disease virus (FMDV), a member of the Picornaviridae, is a pathogen of cloven-hoofed animals and causes a disease of major economic importance. Picornavirus-infected cells show changes in cell morphology and rearrangement of cytoplasmic membranes, which are a consequence of virus replication. We show here, by confocal immunofluorescence and electron microscopy, that the changes in morphology of FMDV-infected cells involve changes in the distribution of microtubule and intermediate filament components during infection. Despite the continued presence of centrosomes in infected cells, there is a loss of tethering of microtubules to the microtubule organizing center (MTOC) region. Loss of labelingfor gamma-tubulin, but not pericentrin, from the MTOC suggests a targeting of gamma-tubulin (or associated proteins) rather than a total breakdown in MTOC structure. The identity of the FMDV protein(s) responsible was determined by the expression of individual viral nonstructural proteins and their precursors in uninfected cells. We report that the only viral nonstructural protein able to reproduce the loss of gamma-tubulin from the MTOC and the loss of integrity of the microtubule system is FMDV 3Cpro. In contrast, infection of cells with another picornavirus, bovine enterovirus, did not affect gamma-tubulin distribution, and the microtubule network remained relatively unaffected.