TRIM35 mediates protection against influenza infection by activating TRAF3 and degrading viral PB2.
A549 Cells
Animals
Apoptosis Regulatory Proteins
/ genetics
DEAD Box Protein 58
/ genetics
Dogs
HEK293 Cells
Humans
Influenza A Virus, H1N1 Subtype
/ genetics
Madin Darby Canine Kidney Cells
Mice
Mice, Knockout
Orthomyxoviridae Infections
/ genetics
Proteolysis
RAW 264.7 Cells
Signal Transduction
/ genetics
THP-1 Cells
TNF Receptor-Associated Factor 3
/ genetics
Ubiquitination
/ immunology
Viral Proteins
/ genetics
PB2
TRAF3
TRIM35
antiviral immunity
influenza A virus
ubiquitination
Journal
Protein & cell
ISSN: 1674-8018
Titre abrégé: Protein Cell
Pays: Germany
ID NLM: 101532368
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
08
04
2020
accepted:
28
04
2020
pubmed:
21
6
2020
medline:
5
2
2021
entrez:
21
6
2020
Statut:
ppublish
Résumé
Tripartite motif (TRIM) family proteins are important effectors of innate immunity against viral infections. Here we identified TRIM35 as a regulator of TRAF3 activation. Deficiency in or inhibition of TRIM35 suppressed the production of type I interferon (IFN) in response to viral infection. Trim35-deficient mice were more susceptible to influenza A virus (IAV) infection than were wild-type mice. TRIM35 promoted the RIG-I-mediated signaling by catalyzing Lys63-linked polyubiquitination of TRAF3 and the subsequent formation of a signaling complex with VISA and TBK1. IAV PB2 polymerase countered the innate antiviral immune response by impeding the Lys63-linked polyubiquitination and activation of TRAF3. TRIM35 mediated Lys48-linked polyubiquitination and proteasomal degradation of IAV PB2, thereby antagonizing its suppression of TRAF3 activation. Our in vitro and in vivo findings thus reveal novel roles of TRIM35, through catalyzing Lys63- or Lys48-linked polyubiquitination, in RIG-I antiviral immunity and mechanism of defense against IAV infection.
Identifiants
pubmed: 32562145
doi: 10.1007/s13238-020-00734-6
pii: 10.1007/s13238-020-00734-6
pmc: PMC7719147
doi:
Substances chimiques
Apoptosis Regulatory Proteins
0
PB2 protein, influenza virus
0
TNF Receptor-Associated Factor 3
0
TRIM35 protein, mouse
0
Viral Proteins
0
Ddx58 protein, mouse
EC 3.6.1.-
DEAD Box Protein 58
EC 3.6.4.13
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
894-914Références
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