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- W4313385425 abstract "Abstract The induction of type I interferon (IFN) is critical for antiviral innate immune response. During virus infection, Retinoic acid-inducible gene I (RIG-I) recognizes the viral RNA and activates Mitochondrial antiviral-signaling protein (MAVS). MAVS further triggers downstream signaling to activate Interferon regulatory factor 3 (IRF3) to induce type I IFN. Many viral proteases cleave adapter proteins in the IFN induction pathway, such as HCV NS3/4A cleaving MAVS, as a strategy to evade anti-viral innate immunity. However, it is not clear whether host protease may also regulate IFN induction pathway to control the steadily low expression of IFN in uninfected cells. Here we report that Hepsin (HPN), which belongs to type II transmembrane serine protease family, could inhibit the production of type I IFN during RNA virus infections in several cell-lines. Hepsin expression could be detected in Huh7 and HepG2 hepatocytes but not ubiquitously in all cell types. Knocking-out Hepsin in mouse embryonic fibroblasts resulted in higher expression of IFNβ and interferon response genes (ISGs). Besides, when co-transfected with N-RIG, which is constitutively activating IFNβ expression, Hepsin could decrease IFNβ promoter activity. However, under the expression of IRF3-5D, Hepsin could not reduce IFNβ promoter activity, suggesting that Hepsin might target certain adaptor proteins downstream of RIG-I and upstream of IRF3. We showed an inverse correlation with wild-type Hepsin expression but not the protease-deficient mutant Hepsin in the IFNβ promoter activities . Consequently, these results reveal a novel role of Hepsin in regulating the type I IFN induction pathway in hepatocytes." @default.
- W4313385425 created "2023-01-06" @default.
- W4313385425 creator A5007904172 @default.
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- W4313385425 date "2016-05-01" @default.
- W4313385425 modified "2023-09-27" @default.
- W4313385425 title "The Effect of Hepsin in Interferon Induction Pathways" @default.
- W4313385425 doi "https://doi.org/10.4049/jimmunol.196.supp.202.34" @default.
- W4313385425 hasPublicationYear "2016" @default.
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