2. Academic Validation
  3. CMPK2 is a host restriction factor that inhibits infection of multiple coronaviruses in a cell-intrinsic manner

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

  • PLoS Biol. 2023 Mar 17;21(3):e3002039. doi: 10.1371/journal.pbio.3002039.
Mingjun Zhu 1 2 3,  Jiahuang Lv 1 2 3 4,  Wei Wang 1 2 3,  Rongli Guo 1 2 3,  Chunyan Zhong 1 2 3 5,  Avan Antia 6,  Qiru Zeng 6,  Jizong Li 1 2 3,  Qingtao Liu 1 2 3,  Jinzhu Zhou 1 2 3,  Xuejiao Zhu 1 2 3,  Baochao Fan 1 2 3,  Siyuan Ding 6,  Bin Li 1 2 3
Affiliations

Affiliations

  • 1 Key Laboratory of Veterinary Biological Engineering and Technology Ministry of Agriculture, Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Nanjing, Jiangsu, China.
  • 2 Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation Base of Ministry of Science and Technology, Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences; Nanjing, Jiangsu, China.
  • 3 Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, Jiangsu, China.
  • 4 College of Animal Science, Tibet Agricultural and Animal Husbandry University College of Veterinary Medicine, Nyingchi, Tibet, China.
  • 5 Biological Engineering Department, Southwest Guizhou Vocational and Technical College for Nationalities, Xingyi, China.
  • 6 Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, United States of America.
PMID: 36930652 DOI: 10.1371/journal.pbio.3002039
Abstract

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.

Figures
Products