• Authors: Xing J. et al.
  • Year: 2021
  • Journal: Nat Commun. 12
  • Applications: in vitro / DNA / jetOPTIMUS
  • Cell type: HEK-293T
    Description: Human embryonic kidney Fibroblast
    Known as: HEK293T, 293T


HEK 293 T cells were transfected with the IFN-β luciferase reporter (IFN-β-Luc), TK-renilla, and HA-PARP9 plasmid or HA-vector by jetOPTIMUS DNA transfection reagent (Polyplus transfection) as per the manufacturer’s instructions. At 20 h after transfection, cells were left stimulated or stimulated for 10 h with LPIC, or viral dsRNA including Reo1187, Reo1198, Reo1320, and Reo1410 (1 μg/ml).


Innate immune cells are critical in protective immunity against viral infections, involved in sensing foreign viral nucleic acids. Here we report that the poly(ADP-ribose) polymerase 9 (PARP9), a member of PARP family, serves as a non-canonical sensor for RNA virus to initiate and amplify type I interferon (IFN) production. We find knockdown or deletion of PARP9 in human or mouse dendritic cells and macrophages inhibits type I IFN production in response to double strand RNA stimulation or RNA virus infection. Furthermore, mice deficient for PARP9 show enhanced susceptibility to infections with RNA viruses because of the impaired type I IFN production. Mechanistically, we show that PARP9 recognizes and binds viral RNA, with resultant recruitment and activation of the phosphoinositide 3-kinase (PI3K) and AKT3 pathway, independent of mitochondrial antiviral-signaling (MAVS). PI3K/AKT3 then activates the IRF3 and IRF7 by phosphorylating IRF3 at Ser385 and IRF7 at Ser437/438 mediating type I IFN production. Together, we reveal a critical role for PARP9 as a non-canonical RNA sensor that depends on the PI3K/AKT3 pathway to produce type I IFN. These findings may have important clinical implications in controlling viral infections and viral-induced diseases by targeting PARP9.