PDF(Pubmed)
Abstract：
African swine fever virus (ASFV) infection is characterized by a progressive decrease in cellular protein synthesis with a concomitant increase in viral protein synthesis, though the mechanism by which the virus achieves this is still unknown. Decrease of cellular mRNA is observed during ASFV infection, suggesting that inhibition of cellular proteins is due to an active mRNA degradation process. ASFV carries a gene (Ba71V D250R/Malawi g5R) that encodes a decapping protein (ASFV-DP) that has a Nudix hydrolase motif and decapping activity in vitro Here, we show that ASFV-DP was expressed from early times and accumulated throughout the infection with a subcellular localization typical of the endoplasmic reticulum, colocalizing with the cap structure and interacting with the ribosomal protein L23a. ASFV-DP was capable of interaction with poly(A) RNA in cultured cells, primarily mediated by the N-terminal region of the protein. ASFV-DP also interacted with viral and cellular RNAs in the context of infection, and its overexpression in infected cells resulted in decreased levels of both types of transcripts. This study points to ASFV-DP as a viral decapping enzyme involved in both the degradation of cellular mRNA and the regulation of viral transcripts.IMPORTANCE Virulent ASFV strains cause a highly infectious and lethal disease in domestic pigs for which there is no vaccine. Since 2007, an outbreak in the Caucasus region has spread to Russia, jeopardizing the European pig population and making it essential to deepen knowledge about the virus. Here, we demonstrate that ASFV-DP is a novel RNA-binding protein implicated in the regulation of mRNA metabolism during infection, making it a good target for vaccine development.
摘要：
非洲猪瘟病毒（ASFV）感染的特征是细胞蛋白合成逐渐减少，病毒蛋白合成随之增加，尽管病毒实现这一目标的机制仍然未知。在ASFV感染期间观察到细胞mRNA的减少，这表明细胞蛋白质的抑制是由于活跃的mRNA降解过程。ASFV携带一个基因（Ba71VD250R/马拉维g5R），该基因编码一种脱盖蛋白（ASFV-DP），该蛋白具有Nudix水解酶基序和体外脱盖活性，我们显示ASFV-DP从早期就表达，并在整个感染过程中积累，具有典型的内质网亚细胞定位，与帽结构共定位并与核糖体蛋白L23a相互作用。ASFV-DP能够与培养细胞中的poly（A）RNA相互作用，主要由蛋白质的N末端区域介导。在感染的情况下，ASFV-DP也与病毒和细胞RNA相互作用，其在感染细胞中的过表达导致两种类型的转录物水平降低。这项研究指出ASFV-DP是一种病毒脱酶，参与细胞mRNA的降解和病毒转录本的调节。重要性毒力ASFV毒株在没有疫苗的家猪中引起高度传染性和致死性疾病。自2007年以来，高加索地区的疫情已经蔓延到俄罗斯，危害欧洲猪种群，并使加深对该病毒的了解变得至关重要。这里,我们证明ASFV-DP是一种新的RNA结合蛋白，与感染过程中mRNA代谢的调节有关。使其成为疫苗开发的良好目标。
