Jagdeo Julienne M, Dufour Antoine, Fung Gabriel, Luo Honglin, Kleifeld Oded, Overall Christopher M, Jan Eric
J Virol. 2015 Jul;89(14):7064-78. doi: 10.1128/JVI.02977-14.
Picornavirus infection involves a dynamic interplay of host and viral protein interactions that modulates cellular processes to facilitate virus infection and evade host antiviral defenses. Here, using a proteomics-based approach known as TAILS to identify protease-generated neo-N-terminal peptides, we identify a novel target of the poliovirus 3C proteinase, the heterogeneous nuclear ribonucleoproteinM(hnRNP M), a nucleocytoplasmic shuttling RNA-binding protein that is primarily known for its role in pre-mRNA splicing. hnRNPMis cleaved in vitro by poliovirus and coxsackievirus B3 (CVB3) 3C proteinases and is targeted in poliovirus- and CVB3-infected HeLa cells and in the hearts of CVB3-infected mice. hnRNPMrelocalizes from the nucleus to the cytoplasm during poliovirus infection. Finally, depletion of hnRNPMusing small interfering RNA knockdown approaches decreases poliovirus and CVB3 infections in HeLa cells and does not affect poliovirus internal ribosome entry site translation and viral RNA stability. We propose that cleavage of and subverting the function of hnRNPMis a general strategy utilized by picornaviruses to facilitate viral infection.
Enteroviruses, a member of the picornavirus family, are RNA viruses that cause a range of diseases, including respiratory ailments, dilated cardiomyopathy, and paralysis. Although enteroviruses have been studied for several decades, the molecular basis of infection and the pathogenic mechanisms leading to disease are still poorly understood. Here, we identify hnRNPMas a novel target of a viral proteinase. We demonstrate that the virus subverts the function of hnRNPMand redirects it to a step in the viral life cycle. We propose that cleavage of hnRNPMis a general strategy that picornaviruses use to facilitate infection.
小RNA病毒感染涉及宿主与病毒蛋白相互作用的动态相互作用，这种相互作用调节细胞过程以促进病毒感染并逃避宿主抗病毒防御。在这里，我们使用一种基于蛋白质组学的方法TAILS来鉴定蛋白酶产生的新N端肽，从而鉴定出脊髓灰质炎病毒3C蛋白酶的一个新靶点——异质性核核糖核蛋白M（hnRNP M），它是一种穿梭于核质之间的RNA结合蛋白，主要因其在mRNA前体剪接中的作用而为人所知。hnRNP M在体外被脊髓灰质炎病毒和柯萨奇病毒B3（CVB3）的3C蛋白酶切割，并且在脊髓灰质炎病毒和CVB3感染的HeLa细胞以及CVB3感染小鼠的心脏中成为靶点。在脊髓灰质炎病毒感染期间，hnRNP M从细胞核重新定位到细胞质。最后，使用小干扰RNA敲低方法耗尽hnRNP M可减少HeLa细胞中脊髓灰质炎病毒和CVB3的感染，并且不影响脊髓灰质炎病毒内部核糖体进入位点的翻译和病毒RNA的稳定性。我们提出，切割hnRNP M并破坏其功能是小RNA病毒用来促进病毒感染的一种普遍策略。
肠道病毒是小RNA病毒家族的成员，是引起一系列疾病的RNA病毒，包括呼吸道疾病、扩张型心肌病和瘫痪。尽管对肠道病毒已经研究了几十年，但感染的分子基础和导致疾病的致病机制仍然知之甚少。在这里，我们鉴定出hnRNP M是病毒蛋白酶的一个新靶点。我们证明病毒破坏了hnRNP M的功能，并将其重定向到病毒生命周期的一个步骤。我们提出，切割hnRNP M是小RNA病毒用来促进感染的一种普遍策略。
