Encephalomyocarditis Virus Abrogates the Interferon Beta Signaling Pathway via Its Structural Protein VP2.
Adaptor Proteins, Signal Transducing
/ metabolism
Capsid Proteins
/ chemistry
Cardiovirus Infections
/ immunology
DEAD Box Protein 58
/ antagonists & inhibitors
Encephalomyocarditis virus
/ genetics
HEK293 Cells
Humans
Immune Evasion
Immunity, Innate
Interferon Type I
/ metabolism
Interferon-Induced Helicase, IFIH1
/ metabolism
Interferon-beta
/ metabolism
Mutation
Protein Interaction Domains and Motifs
Protein Serine-Threonine Kinases
/ metabolism
Receptors, Immunologic
/ antagonists & inhibitors
Signal Transduction
Virus Replication
encephalomyocarditis virus
interferon beta signaling pathway
structural protein
Journal
Journal of virology
ISSN: 1098-5514
Titre abrégé: J Virol
Pays: United States
ID NLM: 0113724
Informations de publication
Date de publication:
24 02 2021
24 02 2021
Historique:
received:
06
08
2020
accepted:
21
11
2020
pubmed:
18
12
2020
medline:
6
5
2021
entrez:
17
12
2020
Statut:
epublish
Résumé
Type I interferon (IFN)-mediated antiviral responses are critical for modulating host-virus responses, and indeed, viruses have evolved strategies to antagonize this pathway. Encephalomyocarditis virus (EMCV) is an important zoonotic pathogen, which causes myocarditis, encephalitis, neurological disease, reproductive disorders, and diabetes in pigs. This study aims to understand how EMCV interacts with the IFN pathway. EMCV circumvents the type I IFN response by expressing proteins that antagonize cellular innate immunity. Here, we show that EMCV VP2 is a negative regulator of the IFN-β pathway. This occurs via the degradation of the MDA5-mediated cytoplasmic double-stranded RNA (dsRNA) antiviral sensing RIG-I-like receptor (RLR) pathway. We show that structural protein VP2 of EMCV interacts with MDA5, MAVS, and TBK1 through its C terminus. In addition, we found that EMCV VP2 could significantly degrade RLRs by the proteasomal and lysosomal pathways. For the first time, EMCV VP2 was shown to play an important role in EMCV evasion of the type I IFN signaling pathway. This study expands our understanding that EMCV utilizes its capsid protein VP2 to evade the host antiviral response.
Identifiants
pubmed: 33328314
pii: JVI.01590-20
doi: 10.1128/JVI.01590-20
pmc: PMC8094936
pii:
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Capsid Proteins
0
Interferon Type I
0
MAVS protein, human
0
Receptors, Immunologic
0
Interferon-beta
77238-31-4
Protein Serine-Threonine Kinases
EC 2.7.11.1
TBK1 protein, human
EC 2.7.11.1
RIGI protein, human
EC 3.6.1.-
IFIH1 protein, human
EC 3.6.1.-
DEAD Box Protein 58
EC 3.6.4.13
Interferon-Induced Helicase, IFIH1
EC 3.6.4.13
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2021 American Society for Microbiology.
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