Rhinovirus 3C protease facilitates specific nucleoporin cleavage and mislocalisation of nuclear proteins in infected host cells.
Rhinovirus 3C protease facilitates specific nucleoporin cleavage and mislocalisation of nuclear proteins in infected host cells.
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DOI：
10.1371/journal.pone.0071316
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Ghildyal R
中科院分区：
文献类型：
--
作者：
Walker EJ;Younessi P;Fulcher AJ;McCuaig R;Thomas BJ;Bardin PG;Jans DA;Ghildyal R
人鼻病毒（HRV）感染导致基本细胞过程的关闭，部分地通过由构成宿主细胞核孔的核孔蛋白（Nups）的切割破坏核质转运。虽然HRV基因组编码两种蛋白酶（2A和3C），能够切割宿主蛋白，如Nup62，很少有人知道的具体贡献。在这里，我们使用转染以及HRV感染的细胞，以建立第一次，3C蛋白酶是最有可能的调解人的切割Nup153在HRV感染，而Nup62和Nup98可能是目标的HRV 2A蛋白酶。HRV 16 3C蛋白酶也能够引起转染细胞中核斑点蛋白SC 35的外观和分布的变化，暗示它是HRV 16感染细胞中SC 35错误定位的关键介质。此外，3C蛋白酶的活性导致核仁的核仁蛋白的重新分配，但不影响核定位的hnRNP蛋白，这意味着核质运输的完全中断导致重新定位的hnRNP蛋白从细胞核到细胞质中的HRV感染的细胞几乎肯定需要2A除了3C蛋白酶。因此，HRV 3C蛋白酶在宿主细胞核蛋白的裂解和错误定位中的特定作用，与2A一致，首次涉及HRV发病机制。
Human Rhinovirus (HRV) infection results in shut down of essential cellular processes, in part through disruption of nucleocytoplasmic transport by cleavage of the nucleoporin proteins (Nups) that make up the host cell nuclear pore. Although the HRV genome encodes two proteases (2A and 3C) able to cleave host proteins such as Nup62, little is known regarding the specific contribution of each. Here we use transfected as well as HRV-infected cells to establish for the first time that 3C protease is most likely the mediator of cleavage of Nup153 during HRV infection, while Nup62 and Nup98 are likely to be targets of HRV2A protease. HRV16 3C protease was also able to elicit changes in the appearance and distribution of the nuclear speckle protein SC35 in transfected cells, implicating it as a key mediator of the mislocalisation of SC35 in HRV16-infected cells. In addition, 3C protease activity led to the redistribution of the nucleolin protein out of the nucleolus, but did not affect nuclear localisation of hnRNP proteins, implying that complete disruption of nucleocytoplasmic transport leading to relocalisation of hnRNP proteins from the nucleus to the cytoplasm in HRV-infected cells almost certainly requires 2A in addition to 3C protease. Thus, a specific role for HRV 3C protease in cleavage and mislocalisation of host cell nuclear proteins, in concert with 2A, is implicated for the first time in HRV pathogenesis.
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DOI：
10.1016/j.bbamcr.2011.03.019
发表时间：
2011-12
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Fulcher AJ;Jans DA
通讯作者：
Jans DA
影响因子：
5.4
作者：
Cancio-Lonches, Clotilde;Yocupicio-Monroy, Martha;Lorena Gutierrez-Escolano, Ana
通讯作者：
Lorena Gutierrez-Escolano, Ana
影响因子：
5.4
作者：
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通讯作者：
Agol, VI
影响因子：
14.9
作者：
Brunel, F;Zakin, MM;Buckle, M
通讯作者：
Buckle, M
DOI：
10.1016/j.bbapap.2007.08.021
发表时间：
2008-01-01
影响因子：
3.2
作者：
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通讯作者：
Jans, David A.