Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de, Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, México.
Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de, Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, México
J Virol. 2018 Jan 2;92(2). doi: 10.1128/JVI.01809-17. Print 2018 Jan 15.
Astroviruses, members of the family , represent an important cause of human gastroenteritis in the world. The cellular factors required for astrovirus replication have been poorly studied. In this work, we evaluated the relevance of the ubiquitin-proteasome system (UPS) in the replication of Yuc8, a human astrovirus serotype 8 strain. We found that proteasome inhibitors decrease the production of infectious viral progeny at a step in the replication cycle subsequent to virus entry. The inhibition of proteasome activity decreases viral RNA levels and viral protein synthesis; similarly, the inhibition of ubiquitination by chemical inhibitors or RNA interference (RNAi) reduces the production of viral progeny as well as viral protein synthesis. The effect on viral progeny production induced by proteasome inhibitors is not explained by a reduction in the pool of monoubiquitin or the induction of early apoptosis or autophagy. Our observations are consistent with the need of the proteolytic activity of the UPS for the efficient replication of the virus and suggest that UPS is necessary for the production of genomic and subgenomic RNA but not for antigenomic RNA. Astroviruses are a major cause of gastroenteritis in young humans and animals, and recently, it was associated with fatal encephalitis in humans. The role of the ubiquitin-proteasome system in the replication of these viruses has not been studied previously. In this work, we present evidence that supports that the proteolytic activity of the proteasome is necessary for efficient viral progeny production and that this proteolytic system is required for the accumulation of both genomic and subgenomic viral RNAs.
星状病毒属于，是世界范围内引起人类胃肠炎的重要病原体。然而，星状病毒复制所需的细胞因子仍知之甚少。在本研究中，我们评估了泛素-蛋白酶体系统（UPS）在 Yuc8（人星状病毒 8 型）复制中的相关性。结果发现，蛋白酶体抑制剂在病毒进入细胞后的复制周期步骤中，降低了感染性病毒后代的产生。蛋白酶体活性的抑制降低了病毒 RNA 水平和病毒蛋白的合成；同样，通过化学抑制剂或 RNA 干扰（RNAi）抑制泛素化，也降低了病毒后代的产生和病毒蛋白的合成。蛋白酶体抑制剂对病毒后代产生的影响不能用单泛素化水平降低或早期细胞凋亡或自噬诱导来解释。我们的观察结果与 UPS 的蛋白水解活性对于病毒有效复制的必要性一致，并表明 UPS 对于基因组和亚基因组 RNA 的产生是必需的，但对于反基因组 RNA 不是必需的。星状病毒是导致人类和动物胃肠炎的主要病原体之一，最近还与人类致命性脑炎有关。然而，此前尚未研究泛素-蛋白酶体系统在这些病毒复制中的作用。本研究提供了证据表明，蛋白酶体的蛋白水解活性对于有效产生病毒后代是必需的，并且该蛋白酶体系统对于基因组和亚基因组病毒 RNA 的积累都是必需的。
