In:
PLOS Biology, Public Library of Science (PLoS), Vol. 21, No. 3 ( 2023-3-17), p. e3002039-
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.
Type of Medium:
Online Resource
ISSN:
1545-7885
DOI:
10.1371/journal.pbio.3002039
DOI:
10.1371/journal.pbio.3002039.g001
DOI:
10.1371/journal.pbio.3002039.g002
DOI:
10.1371/journal.pbio.3002039.g003
DOI:
10.1371/journal.pbio.3002039.g004
DOI:
10.1371/journal.pbio.3002039.g005
DOI:
10.1371/journal.pbio.3002039.g006
DOI:
10.1371/journal.pbio.3002039.g007
DOI:
10.1371/journal.pbio.3002039.g008
DOI:
10.1371/journal.pbio.3002039.g009
DOI:
10.1371/journal.pbio.3002039.s001
DOI:
10.1371/journal.pbio.3002039.s002
DOI:
10.1371/journal.pbio.3002039.s003
DOI:
10.1371/journal.pbio.3002039.s004
DOI:
10.1371/journal.pbio.3002039.s005
DOI:
10.1371/journal.pbio.3002039.s006
DOI:
10.1371/journal.pbio.3002039.s007
DOI:
10.1371/journal.pbio.3002039.s008
DOI:
10.1371/journal.pbio.3002039.s009
DOI:
10.1371/journal.pbio.3002039.s010
DOI:
10.1371/journal.pbio.3002039.s011
DOI:
10.1371/journal.pbio.3002039.s012
DOI:
10.1371/journal.pbio.3002039.s013
DOI:
10.1371/journal.pbio.3002039.s014
DOI:
10.1371/journal.pbio.3002039.s015
DOI:
10.1371/journal.pbio.3002039.s016
DOI:
10.1371/journal.pbio.3002039.s017
DOI:
10.1371/journal.pbio.3002039.s018
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2126773-X
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