CMPK2 is a host restriction factor that inhibits infection of multiple coronaviruses in a cell-intrinsic manner

文献类型： 外文期刊

第一作者： Zhu, Mingjun

作者： Zhu, Mingjun;Lv, Jiahuang;Wang, Wei;Guo, Rongli;Zhong, Chunyan;Li, Jizong;Liu, Qingtao;Zhou, Jinzhu;Zhu, Xuejiao;Fan, Baochao;Li, Bin;Zhu, Mingjun;Lv, Jiahuang;Wang, Wei;Guo, Rongli;Zhong, Chunyan;Li, Jizong;Liu, Qingtao;Zhou, Jinzhu;Zhu, Xuejiao;Fan, Baochao;Li, Bin;Zhu, Mingjun;Lv, Jiahuang;Wang, Wei;Guo, Rongli;Zhong, Chunyan;Li, Jizong;Liu, Qingtao;Zhou, Jinzhu;Zhu, Xuejiao;Fan, Baochao;Li, Bin;Lv, Jiahuang;Zhong, Chunyan;Antia, Avan;Zeng, Qiru;Ding, Siyuan

作者机构：

期刊名称：PLOS BIOLOGY （ 影响因子：9.8； 五年影响因子：9.2 ）

ISSN： 1544-9173

年卷期： 2023 年 21 卷 3 期

页码：

收录情况： SCI

摘要： Coronaviruses (CoVs) comprise a group of important human and animal pathogens. Despite extensive research in the past 3 years, the host innate immune defense mechanisms against CoVs remain incompletely understood, limiting the development of effective antivirals and non-antibody-based therapeutics. Here, we performed an integrated transcriptomic analysis of porcine jejunal epithelial cells infected with porcine epidemic diarrhea virus (PEDV) and identified cytidine/uridine monophosphate kinase 2 (CMPK2) as a potential host restriction factor. CMPK2 exhibited modest antiviral activity against PEDV infection in multiple cell types. CMPK2 transcription was regulated by interferon-dependent and interferon regulatory factor 1 (IRF1)-dependent pathways post-PEDV infection. We demonstrated that 3 '-deoxy-3 ',4 '-didehydro-cytidine triphosphate (ddhCTP) catalysis by Viperin, another interferon-stimulated protein, was essential for CMPK2's antiviral activity. Both the classical catalytic domain and the newly identified antiviral key domain of CMPK2 played crucial roles in this process. Together, CMPK2, viperin, and ddhCTP suppressed the replication of several other CoVs of different genera through inhibition of the RNA-dependent RNA polymerase activities. Our results revealed a previously unknown function of CMPK2 as a restriction factor for CoVs, implying that CMPK2 might be an alternative target of interfering with the viral polymerase activity.

分类号：

  • 相关文献
作者其他论文 更多>>

微信小程序