| First Author | Yan BR | Year | 2017 |
| Journal | PLoS Pathog | Volume | 13 |
| Issue | 9 | Pages | e1006648 |
| PubMed ID | 28934360 | Mgi Jnum | J:249793 |
| Mgi Id | MGI:5920687 | Doi | 10.1371/journal.ppat.1006648 |
| Citation | Yan BR, et al. (2017) PKACs attenuate innate antiviral response by phosphorylating VISA and priming it for MARCH5-mediated degradation. PLoS Pathog 13(9):e1006648 |
| abstractText | Sensing of viral RNA by RIG-I-like receptors initiates innate antiviral response, which is mediated by the central adaptor VISA. How the RIG-I-VISA-mediated antiviral response is terminated at the late phase of infection is enigmatic. Here we identified the protein kinase A catalytic (PKAC) subunits alpha and beta as negative regulators of RNA virus-triggered signaling in a redundant manner. Viral infection up-regulated cellular cAMP levels and activated PKACs, which then phosphorylated VISA at T54. This phosphorylation abrogated virus-induced aggregation of VISA and primed it for K48-linked polyubiquitination and degradation by the E3 ligase MARCH5, leading to attenuation of virus-triggered induction of downstream antiviral genes. PKACs-deficiency or inactivation by the inhibitor H89 potentiated innate immunity to RNA viruses in cells and mice. Our findings reveal a critical mechanism of attenuating innate immune response to avoid host damage at the late phase of viral infection by the house-keeping PKA kinase. |
