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甲型流感病毒人类毒株复制过程中肌动蛋白细胞骨架的宿主细胞依赖性作用

Host-cell-dependent role of actin cytoskeleton during the replication of a human strain of influenza A virus.

作者信息

Arcangeletti M C, De Conto F, Ferraglia F, Pinardi F, Gatti R, Orlandini G, Covan S, Motta F, Rodighiero I, Dettori G, Chezzi C

机构信息

Microbiology Section, Department of Pathology and Laboratory Medicine, University of Parma, viale Antonio Gramsci 14, 43100 Parma, Italy.

出版信息

Arch Virol. 2008;153(7):1209-21. doi: 10.1007/s00705-008-0103-0. Epub 2008 May 17.

DOI:10.1007/s00705-008-0103-0
PMID:18488136
Abstract

This study was aimed at investigating the possible involvement of the actin cytoskeleton in the modulation of host permissiveness to A/NWS/33 human influenza virus infection in two mammalian (MDCK and LLC-MK2) cell lines in vitro. During the early stages of infection, no appreciable association between incoming NWS/33 virions and cortical actin was detectable in the permissive MDCK model by confocal microscopy, while extensive colocalization and a slower infection progression were observed in LLC-MK2 cells. In the latter model, we also demonstrated the inability of the virus to carry out multiple replication cycles, irrespective of the presence of cleaved HA subunits in the released virions. Treatment with the actin-depolymerizing agent cytochalasin D significantly increased the infection efficiency in LLC-MK2 cells, while a detrimental effect was observed in the MDCK cell line. Our data suggest a selective role of the actin network in inducing a restriction to influenza virus replication, mostly depending on its molecular organization, the host cell type and virus replication phase.

摘要

本研究旨在调查肌动蛋白细胞骨架在体外两种哺乳动物(MDCK和LLC-MK2)细胞系中对宿主对A/NWS/33人流感病毒感染易感性的调节中可能发挥的作用。在感染早期,通过共聚焦显微镜在允许性MDCK模型中未检测到传入的NWS/33病毒粒子与皮质肌动蛋白之间有明显关联,而在LLC-MK2细胞中观察到广泛的共定位以及较慢的感染进程。在后者模型中,我们还证明了病毒无法进行多个复制周期,无论释放的病毒粒子中是否存在裂解的HA亚基。用肌动蛋白解聚剂细胞松弛素D处理可显著提高LLC-MK2细胞的感染效率,而在MDCK细胞系中则观察到有害作用。我们的数据表明,肌动蛋白网络在诱导对流感病毒复制的限制方面具有选择性作用,这主要取决于其分子组织、宿主细胞类型和病毒复制阶段。

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