Department of Microbiology and Molecular Genetics, School of Medicine, University of California, Irvine, CA 92697, USA.
Department of Microbiology and Molecular Genetics, School of Medicine, University of California, Irvine, CA 92697, USA.
Virology. 2018 Mar;516:139-146. doi: 10.1016/j.virol.2018.01.010. Epub 2018 Jan 30.
Cardioviruses cause diseases in many animals including, in rare cases, humans. Although they share common features with all picornaviruses, cardioviruses have unique properties that distinguish them from other family members, including enteroviruses. One feature shared by all picornaviruses is the covalent attachment of VPg to the 5' end of genomic RNA via a phosphotyrosyl linkage. For enteroviruses, this linkage is cleaved by a host cell protein, TDP2. Since TDP2 is divergently required during enterovirus infections, we determined if TDP2 is necessary during infection by the prototype cardiovirus, EMCV. We found that EMCV yields are reduced in the absence of TDP2. We observed a decrease in viral protein accumulation and viral RNA replication in the absence of TDP2. In contrast to enterovirus infections, we found that TDP2 is modified at peak times of EMCV infection. This finding suggests a unique mechanism for cardioviruses to regulate TDP2 activity during infection.
心血管病毒可引起许多动物发病，在极少数情况下也可引起人类发病。虽然它们与所有小核糖核酸病毒具有共同特征，但心血管病毒具有独特的性质，可将其与其他家族成员（包括肠道病毒）区分开来。所有小核糖核酸病毒共有的一个特征是，VPg 通过磷酸酪氨酸键共价连接到基因组 RNA 的 5'端。对于肠道病毒，这种连接由宿主细胞蛋白 TDP2 切割。由于 TDP2 在肠道病毒感染过程中呈分歧性需求，因此我们确定 TDP2 是否是原型心血管病毒 EMCV 感染所必需的。我们发现，在没有 TDP2 的情况下，EMCV 的产量会降低。我们观察到在没有 TDP2 的情况下，病毒蛋白积累和病毒 RNA 复制减少。与肠道病毒感染相反，我们发现 TDP2 在 EMCV 感染的高峰期被修饰。这一发现表明，心血管病毒在感染过程中调节 TDP2 活性的机制是独特的。
