STAT3 Regulates the Type I IFN-Mediated Antiviral Response by Interfering with the Nuclear Entry of STAT1.
Int J Mol Sci
; 20(19)2019 Sep 30.
Article
in En
| MEDLINE
| ID: mdl-31575039
ABSTRACT
Signal transducer and activator of transcription 3 (STAT3) is a multifunctional factor that regulates inflammation and immunity. Knowledge of its regulatory mechanisms is very limited. Here, we showed that enterovirus 71 (EV71) infection induced the phosphorylation of STAT3 and the expression of its downstream inflammatory regulators. Knockdown of STAT3 with siRNAs significantly restricted viral RNA and protein levels, and also reduced viral titers. With further investigation, we found that importin α family member Karyopherin-α1 (KPNA1) was employed by both STAT1 and STAT3 for their nuclear import. The phosphorylated and un-phosphorylated STAT3 competed with STAT1 for binding to the decreased KPNA1 post infection and repressed downstream ISG expression. STAT3 knockdown alleviated the repressed type I IFN-mediated antiviral response upon infection and led to decreased viral replication. Taken together, our data suggested the role of STAT3 in maintaining the balance of inflammation and antiviral responses in the central nervous system (CNS) upon infection.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Virus Diseases
/
Interferon Type I
/
STAT1 Transcription Factor
/
STAT3 Transcription Factor
/
Host-Pathogen Interactions
Limits:
Humans
Language:
En
Journal:
Int J Mol Sci
Year:
2019
Document type:
Article
Affiliation country:
China