CMPK2 is a host restriction factor that inhibits infection of multiple coronaviruses in a cell-intrinsic manner.
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....
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2023-03-01
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| Series: | PLoS Biology |
| Online Access: | https://doi.org/10.1371/journal.pbio.3002039 |
| _version_ | 1827968557623803904 |
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| author | Mingjun Zhu Jiahuang Lv Wei Wang Rongli Guo Chunyan Zhong Avan Antia Qiru Zeng Jizong Li Qingtao Liu Jinzhu Zhou Xuejiao Zhu Baochao Fan Siyuan Ding Bin Li |
| author_facet | Mingjun Zhu Jiahuang Lv Wei Wang Rongli Guo Chunyan Zhong Avan Antia Qiru Zeng Jizong Li Qingtao Liu Jinzhu Zhou Xuejiao Zhu Baochao Fan Siyuan Ding Bin Li |
| author_sort | Mingjun Zhu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-09T18:24:31Z |
| format | Article |
| id | doaj.art-915beadf58584349bc93595cb515aaff |
| institution | Directory Open Access Journal |
| issn | 1544-9173 1545-7885 |
| language | English |
| last_indexed | 2024-04-09T18:24:31Z |
| publishDate | 2023-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj.art-915beadf58584349bc93595cb515aaff2023-04-12T05:30:41ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852023-03-01213e300203910.1371/journal.pbio.3002039CMPK2 is a host restriction factor that inhibits infection of multiple coronaviruses in a cell-intrinsic manner.Mingjun ZhuJiahuang LvWei WangRongli GuoChunyan ZhongAvan AntiaQiru ZengJizong LiQingtao LiuJinzhu ZhouXuejiao ZhuBaochao FanSiyuan DingBin LiCoronaviruses (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.https://doi.org/10.1371/journal.pbio.3002039 |
| spellingShingle | Mingjun Zhu Jiahuang Lv Wei Wang Rongli Guo Chunyan Zhong Avan Antia Qiru Zeng Jizong Li Qingtao Liu Jinzhu Zhou Xuejiao Zhu Baochao Fan Siyuan Ding Bin Li CMPK2 is a host restriction factor that inhibits infection of multiple coronaviruses in a cell-intrinsic manner. PLoS Biology |
| title | CMPK2 is a host restriction factor that inhibits infection of multiple coronaviruses in a cell-intrinsic manner. |
| title_full | CMPK2 is a host restriction factor that inhibits infection of multiple coronaviruses in a cell-intrinsic manner. |
| title_fullStr | CMPK2 is a host restriction factor that inhibits infection of multiple coronaviruses in a cell-intrinsic manner. |
| title_full_unstemmed | CMPK2 is a host restriction factor that inhibits infection of multiple coronaviruses in a cell-intrinsic manner. |
| title_short | CMPK2 is a host restriction factor that inhibits infection of multiple coronaviruses in a cell-intrinsic manner. |
| title_sort | cmpk2 is a host restriction factor that inhibits infection of multiple coronaviruses in a cell intrinsic manner |
| url | https://doi.org/10.1371/journal.pbio.3002039 |
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