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J Virol:中科院武汉病毒所王汉中研究组揭示EV71病毒聚合酶的SUMO化修饰促进病毒复制

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摘要 : 2016年9月7日,国际病毒学领域权威学术期刊《Journalof Virology》在线发表了中国科学院武汉病毒研究所王汉中研究组题为SUMO Modification Stabilizes Enterovirus 71 Polymerase 3D to Facilitate Viral Replication的研究论文,实验师刘艳是论文第一作者,通讯作者为副研究员郑振华。研究发现EV71病毒(肠道病毒71型)的3D聚合酶同时具有SUMO化修饰和泛素化修饰。泛素化修饰依赖于SUMO化修饰,二者能起到稳定聚合酶的作用,从而促进病毒的复制。 SUMO化修饰(Smallubiquitin-like modifier modification, SUMOylation )是一类翻译后修饰,对于细胞内的蛋白和信号途径起到重要的调节作用。病毒的聚合酶在病毒复制过程中至关重要,其上修饰会对病毒的复制具有直接影响。 该研究通过生物信息学分析和定点突变,发现159位的赖氨酸和150-152位(SUMO-interacting motifs, SIMs)的氨基酸为3D的修饰位点,这些位点突变后都会对聚合

2016年9月7日,国际病毒学领域权威学术期刊《Journalof Virology》在线发表了中国科学院武汉病毒研究所王汉中研究组题为“SUMO Modification Stabilizes Enterovirus 71 Polymerase 3D to Facilitate Viral Replication”的研究论文,实验师刘艳是论文第一作者,通讯作者为副研究员郑振华。研究发现ev71病毒(肠道病毒71型)的3D聚合酶同时具有SUMO化修饰和泛素化修饰。泛素化修饰依赖于SUMO化修饰,二者能起到稳定聚合酶的作用,从而促进病毒的复制。

SUMO化修饰(Smallubiquitin-like modifier modification, SUMOylation )是一类翻译后修饰,对于细胞内的蛋白和信号途径起到重要的调节作用。病毒的聚合酶在病毒复制过程中至关重要,其上修饰会对病毒的复制具有直接影响。

该研究通过生物信息学分析和定点突变,发现159位的赖氨酸和150-152位(SUMO-interacting motifs, SIMs)的氨基酸为3D的修饰位点,这些位点突变后都会对聚合酶活性起到一定的破坏作用。而过量表达SUMO-1后感染病毒发现,随着3D的SUMO化修饰的增强,病毒的复制也增加,推测是因为增加聚合酶的稳定性引起的。研究的主要意义在于首次发现EV71聚合酶的SUMO化修饰,为进一步开发针对EV71的药物起到靶点作用。

J Virol:中科院武汉病毒所王汉中研究组揭示EV71病毒聚合酶的SUMO化修饰促进病毒复制
图:SUMO-1修饰能增强病毒的复制

原文链接:

SUMO Modification Stabilizes Enterovirus 71 Polymerase 3D to Facilitate Viral Replication

原文摘要:

Accumulating evidences suggest that viruses hijack cellular proteins to circumvent the host immune system. Ubiquitination and SUMOylation are extensively studied post-translational modifications (PTMs) that play critical roles in diverse biological processes. Crosstalk between ubiquitination and SUMOylation of both host and viral proteins has been reported to result in distinct functional conses1quences. Enterovirus 71 (EV71), an RNA virus belonging toPicornaviridae family, is a common cause of hand, foot and mouth disease. Little is known concerning how host PTM systems interact with enteroviruses. Here, we demonstrated that the 3D protein, an RNA-dependent RNA polymerase (RdRp) of EV71, is modified by small ubiquitin-like modifier-1 both during infection and in vitro. Residues K159 and L150/D151/L152 were responsible for 3D SUMOylation determined by bioinformatic prediction combined with site-directed mutagenesis. And primer-dependent polymerase assays indicated that mutation of SUMOylation sites impaired 3D polymerase activity and virus replication. Moreover, 3D is ubiquitinated in a SUMO-dependent manner, and SUMOylation is crucial for 3D stability which may be due to the interplay between the two PTMs. Of importance, increasing the level of SUMO-1 in EV71-infected cells augmented the SUMOylation and ubiquitination level of 3D, leading to enhanced replication of EV71. These results together suggested that SUMO and ubiquitin cooperatively regulated EV71 infection either by SUMO-ubiquitin hybrid chains or by ubiquitin conjugating to the exposed lysine residue through SUMOylation. Our study provides a new insight into how a virus utilizes cellular pathways to facilitate its replication.

doi:10.1128/JVI.01756-16

作者:王汉中 点击:

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