武汉病毒所发现EV71病毒聚合酶的SUMO化修饰能促进病毒复制

 

近期，中国科学院武汉病毒研究所王汉中研究团队发现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。该论文已在线发表在病毒学权威杂志JournalofVirology上，实验师刘艳是论文第一作者，通讯作者为郑振华副研究员。

 

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-interactingmotifs,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。

 

该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。本研究得到了国家自然科学青年基金的支持。

 

SUMOModificationStabilizesEnterovirus71Polymerase3DtoFacilitateViralReplication

 

ABSTRACT

 

Accumulatingevidencessuggestthatviruseshijackcellularproteinstocircumventthehostimmunesystem.UbiquitinationandSUMOylationareextensivelystudiedpost-translationalmodifications(PTMs)thatplaycriticalrolesindiversebiologicalprocesses.CrosstalkbetweenubiquitinationandSUMOylationofbothhostandviralproteinshasbeenreportedtoresultindistinctfunctionalconses1quences.Enterovirus71(EV71),anRNAvirusbelongingtoPicornaviridaefamily,isacommoncauseofhand,footandmouthdisease.LittleisknownconcerninghowhostPTMsystemsinteractwithenteroviruses.Here,wedemonstratedthatthe3Dprotein,anRNA-dependentRNApolymerase(RdRp)ofEV71,ismodifiedbysmallubiquitin-likemodifier-1bothduringinfectionandinvitro.ResiduesK159andL150/D151/L152wereresponsiblefor3DSUMOylationdeterminedbybioinformaticpredictioncombinedwithsite-directedmutagenesis.Andprimer-dependentpolymeraseassaysindicatedthatmutationofSUMOylationsitesimpaired3Dpolymeraseactivityandvirusreplication.Moreover,3DisubiquitinatedinaSUMO-dependentmanner,andSUMOylationiscrucialfor3DstabilitywhichmaybeduetotheinterplaybetweenthetwoPTMs.Ofimportance,increasingthelevelofSUMO-1inEV71-infectedcellsaugmentedtheSUMOylationandubiquitinationlevelof3D,leadingtoenhancedreplicationofEV71.TheseresultstogethersuggestedthatSUMOandubiquitincooperativelyregulatedEV71infectioneitherbySUMO-ubiquitinhybridchainsorbyubiquitinconjugatingtotheexposedlysineresiduethroughSUMOylation.Ourstudyprovidesanewinsightintohowavirusutilizescellularpathwaystofacilitateitsreplication.