USP18attenuates the anti-hepatitis B virus effect of IFN by down regulating JAK-STAT pathway

Author:

Jiang Wei1ORCID,Wu Dongbo1,Zeng Qingmin1,Liu Cong1,Chen Enqiang1,Bai Lang1,Tang Hong1ORCID

Affiliation:

1. Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, Sichuan, 610041, China

Abstract

Aim: USP18 is a type of IFN-stimulated gene, which is associated with virological responses to IFN therapy in HBV (hepatitis B virus). However, its detailed molecular mechanism needs to be explored. Materials & methods: With HBV replication cells and mouse models, the USP18 was overexpressed or inhibited, followed by treatment with IFN or Poly (I:C). The expressions of HBV DNA, HBsAg, HBeAg and protein factors in the samples were detected. Results: Overexpression of USP18 attenuates anti-HBV effect of IFN in vitro and in vivo by inhibiting JAK-STAT pathway and reducing the expression of MX1 and OAS. While, the inhibition of USP18 can promote to activate JAK-STAT pathway to enhance the antiviral effect of IFN. Conclusion: USP18 negatively regulates the anti-HBV effect of IFN by regulating JAK-STAT pathway. It may provide new insights into innate immunity mechanisms in CHB patients receiving IFN treatment.

Funder

The Science and Technological Supports Project of Sichuan Province, China

Post-Doctor Research Project, West China Hospital, Sichuan University

National Natural Science Foundation of China

1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University

Publisher

Future Medicine Ltd

Subject

Virology

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