Coronavirus Endoribonuclease and Deubiquitinating Interferon Antagonists Differentially Modulate the Host Response during Replication in Macrophages.
Animals
Computational Biology
Coronavirus
/ physiology
Coronavirus Infections
/ genetics
Cytokines
/ metabolism
Endoribonucleases
/ metabolism
Gene Expression Profiling
Host-Pathogen Interactions
/ genetics
Inflammation Mediators
/ metabolism
Interferons
/ metabolism
Macrophages
/ immunology
Mice
Models, Biological
Mutation
RNA, Viral
Unfolded Protein Response
Viral Nonstructural Proteins
/ metabolism
Virus Replication
EndoU
IFN antagonist
PLP2
coronavirus
nsp15
papain-like protease
transcriptomic profiling
Journal
Journal of virology
ISSN: 1098-5514
Titre abrégé: J Virol
Pays: United States
ID NLM: 0113724
Informations de publication
Date de publication:
18 05 2020
18 05 2020
Historique:
received:
06
02
2020
accepted:
09
03
2020
pubmed:
20
3
2020
medline:
12
9
2020
entrez:
20
3
2020
Statut:
epublish
Résumé
Coronaviruses (CoVs) encode multiple interferon (IFN) antagonists that modulate the host response to virus replication. Here, we evaluated the host transcriptional response to infection with murine coronaviruses encoding independent mutations in one of two different viral antagonists, the deubiquitinase (DUB) within nonstructural protein 3 or the endoribonuclease (EndoU) within nonstructural protein 15. We used transcriptomics approaches to compare the scope and kinetics of the host response to the wild-type (WT), DUBmut, and EndoUmut viruses in infected macrophages. We found that the EndoUmut virus activates a focused response that predominantly involves type I interferons and interferon-related genes, whereas the WT and DUBmut viruses more broadly stimulate upregulation of over 2,800 genes, including networks associated with activating the unfolded protein response (UPR) and the proinflammatory response associated with viral pathogenesis. This study highlights the role of viral interferon antagonists in shaping the kinetics and magnitude of the host response during virus infection and demonstrates that inactivating a dominant viral antagonist, the coronavirus endoribonuclease, dramatically alters the host response in macrophages.
Identifiants
pubmed: 32188729
pii: JVI.00178-20
doi: 10.1128/JVI.00178-20
pmc: PMC7269425
pii:
doi:
Substances chimiques
Cytokines
0
Inflammation Mediators
0
RNA, Viral
0
Viral Nonstructural Proteins
0
Interferons
9008-11-1
Endoribonucleases
EC 3.1.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAID NIH HHS
ID : R01 AI085089
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI007508
Pays : United States
Informations de copyright
Copyright © 2020 American Society for Microbiology.
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