生物
解旋酶
聚合酶
DNA复制
冠状病毒
蛋白质亚单位
病毒学
DNA聚合酶
病毒复制
细胞生物学
免疫沉淀
RNA聚合酶
核糖核酸
分子生物学
病毒
DNA
基因
遗传学
2019年冠状病毒病(COVID-19)
传染病(医学专业)
病理
医学
疾病
作者
Li Quan,Xinxin Sun,Luzhou Xu,Rui Ai Chen,Ding Xiang Liu
标识
DOI:10.1080/22221751.2023.2176008
摘要
Disruption of the cell cycle is a common strategy shared by many viruses to create a conducible cellular microenvironment for their efficient replication. We have previously shown that infection of cells with gammacoronavirus infectious bronchitis virus (IBV) activated the theataxia-telangiectasia mutated (ATM) Rad3-related (ATR)/checkpoint kinase 1 (Chk1) pathway and induced cell cycle arrest in S and G2/M phases, partially through the interaction of nonstructural protein 13 (nsp13) with the p125 catalytic subunit of DNA polymerase delta (pol δ). In this study, we show, by GST pulldown, co-immunoprecipitation and immunofluorescent staining, that IBV nsp12 directly interacts with the p50 regulatory subunit of pol δ in vitro and in cells overexpressing the two proteins as well as in cells infected with a recombinant IBV harbouring an HA-tagged nsp12. Furthermore, nsp12 from severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2 was also able to interact with p50. These interactions play a synergistic role with nsp13 in the induction of S phase arrest. The fact that subunits of an essential cellular DNA replication machinery physically associate with two core replication enzymes from three different coronaviruses highlights the importance of these associations in coronavirus replication and virus-host interaction, and reveals the potential of targeting these subunits for antiviral intervention.
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