Abstract
In response to viral infection, RIG-I-like RNA helicases detect viral RNA and signal through the mitochondrial adapter protein VISA. VISA activation leads to rapid activation of transcription factors IRF3 and NF-κB, which collaborate to induce transcription of type I interferon (IFN) genes and cellular antiviral response. It has been demonstrated that VISA is activated by forming prion-like aggregates. However, how this process is regulated remains unknown. Here we show that overexpression of HSC71 resulted in potent inhibition of virus-triggered transcription of IFNB1 gene and cellular antiviral response. Consistently, knockdown of HSC71 had opposite effects. HSC71 interacted with VISA, and negatively regulated virus-triggered VISA aggregation. These findings suggest that HSC71 functions as a check against VISA-mediated antiviral response.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adaptor Proteins, Signal Transducing / biosynthesis*
-
Adaptor Proteins, Signal Transducing / chemistry
-
Adaptor Proteins, Signal Transducing / genetics*
-
Adaptor Proteins, Signal Transducing / metabolism
-
Cell Aggregation / genetics
-
GPI-Linked Proteins / metabolism
-
Gene Knockdown Techniques
-
HEK293 Cells
-
HSC70 Heat-Shock Proteins / genetics*
-
HSC70 Heat-Shock Proteins / metabolism
-
Heat-Shock Response / genetics
-
Humans
-
Interferon Regulatory Factor-3 / genetics
-
Interferon Regulatory Factor-3 / metabolism
-
Interferon-beta / genetics
-
NF-kappa B / genetics
-
Prions / metabolism
-
Receptors, Retinoic Acid / metabolism
-
Viruses / drug effects
-
Viruses / metabolism*
-
Viruses / pathogenicity
Substances
-
Adaptor Proteins, Signal Transducing
-
GPI-Linked Proteins
-
HSC70 Heat-Shock Proteins
-
HSPA8 protein, human
-
IRF3 protein, human
-
Interferon Regulatory Factor-3
-
MAVS protein, human
-
NF-kappa B
-
PLAAT4 protein, human
-
PRND protein, human
-
Prions
-
Receptors, Retinoic Acid
-
Interferon-beta