SARS-CoV-2 N Protein Targets TRIM25-Mediated RIG-I Activation to Suppress Innate Immunity.
COVID-19
/ genetics
Coronavirus Nucleocapsid Proteins
/ genetics
DEAD Box Protein 58
/ genetics
Gene Expression Regulation
Host-Pathogen Interactions
Humans
Immunity, Innate
Interferon-beta
/ genetics
Promoter Regions, Genetic
Receptors, Immunologic
/ genetics
SARS-CoV-2
/ genetics
Signal Transduction
Transcription Factors
/ genetics
Tripartite Motif Proteins
/ genetics
Ubiquitin-Protein Ligases
/ genetics
RIG-I activation
SARS-CoV-2 N protein
innate immunity
Journal
Viruses
ISSN: 1999-4915
Titre abrégé: Viruses
Pays: Switzerland
ID NLM: 101509722
Informations de publication
Date de publication:
23 07 2021
23 07 2021
Historique:
received:
22
06
2021
revised:
19
07
2021
accepted:
22
07
2021
entrez:
28
8
2021
pubmed:
29
8
2021
medline:
11
9
2021
Statut:
epublish
Résumé
A weak production of INF-β along with an exacerbated release of pro-inflammatory cytokines have been reported during infection by the novel SARS-CoV-2 virus. SARS-CoV-2 encodes several proteins able to counteract the host immune system, which is believed to be one of the most important features contributing to the viral pathogenesis and development of a severe clinical picture. Previous reports have demonstrated that SARS-CoV-2 N protein, along with some non-structural and accessory proteins, efficiently suppresses INF-β production by interacting with RIG-I, an important pattern recognition receptor (PRR) involved in the recognition of pathogen-derived molecules. In the present study, we better characterized the mechanism by which the SARS-CoV-2 N counteracts INF-β secretion and affects RIG-I signaling pathways. In detail, when the N protein was ectopically expressed, we noted a marked decrease in TRIM25-mediated RIG-I activation. The capability of the N protein to bind to, and probably mask, TRIM25 could be the consequence of its antagonistic activity. Furthermore, this interaction occurred at the SPRY domain of TRIM25, harboring the RNA-binding activity necessary for TRIM25 self-activation. Here, we describe new findings regarding the interplay between SARS-CoV-2 and the IFN system, filling some gaps for a better understanding of the molecular mechanisms affecting the innate immune response in COVID-19.
Identifiants
pubmed: 34452305
pii: v13081439
doi: 10.3390/v13081439
pmc: PMC8402637
pii:
doi:
Substances chimiques
Coronavirus Nucleocapsid Proteins
0
Receptors, Immunologic
0
Transcription Factors
0
Tripartite Motif Proteins
0
Interferon-beta
77238-31-4
TRIM25 protein, human
EC 2.3.2.27
Ubiquitin-Protein Ligases
EC 2.3.2.27
RIGI protein, human
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
Subventions
Organisme : Istituto di Ricerca Virologica Oretta Bartolomei Corsi
ID : 0027603
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