Hepatitis B Virus e Antigen Activates the Suppressor of Cytokine Signaling 2 to Repress Interferon Action

Scientific Reports
Yi YuJianguo Wu

Abstract

Hepatitis B virus (HBV) infection causes acute hepatitis B (AHB), chronic hepatitis B (CHB), liver cirrhosis (LC), and eventually hepatocellular carcinoma (HCC). The presence of hepatitis B e antigen (HBeAg) in the serum generally indicates ongoing viral replication and disease progression. However, the mechanism by which HBeAg regulates HBV infection remains unclear. Interferons (IFNs) are pleiotropic cytokines that participate in host innate immunity. After binding to receptors, IFNs activate the JAK/STAT pathway to stimulate expression of IFN-stimulated genes (ISGs), leading to induction of antiviral responses. Here, we revealed that HBeAg represses IFN/JAK/STAT signaling to facilitate HBV replication. Initially, HBeAg stimulates the expression of suppressor of cytokine signaling 2 (SOCS2). Subsequently, SOCS2 impairs IFN/JAK/STAT signaling through reducing the stability of tyrosine kinase 2 (TYK2), downregulating the expression of type I and III IFN receptors, attenuating the phosphorylation and nucleus translocation of STAT1. Finally, SOCS2 inhibits the expression of ISGs, which leads to the repression of IFN action and facilitation of viral replication. These results demonstrate an important role of HBeAg in the regulatio...Continue Reading

References

Apr 1, 1992·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·G FattovichG Busatto
Apr 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·G R FosterG R Stark
Aug 1, 1989·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·M R BrunettoF Bonino
Jul 24, 1981·Science·P TiollaisG N Vyas
May 30, 1996·The New England Journal of Medicine·C NiederauD Häussinger
Jun 26, 1997·Nature·R StarrD J Hilton
Mar 8, 2000·Microbiology and Molecular Biology Reviews : MMBR·C Seeger, W S Mason
Jun 1, 2000·Proceedings of the National Academy of Sciences of the United States of America·S E NicholsonM Baca
Apr 28, 2001·Cytokine & Growth Factor Reviews·D E Levy, A García-Sastre
Oct 5, 2001·Clinical Microbiology Reviews·C E Samuel
Dec 7, 2002·Nature Immunology·Paul SheppardKevin M Klucher
Dec 17, 2002·Nature Immunology·Sergei V KotenkoRaymond P Donnelly
Oct 28, 2003·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·David Milich, T Jake Liang
Mar 12, 2004·The New England Journal of Medicine·Don Ganem, Alfred M Prince
Apr 22, 2004·Proceedings of the National Academy of Sciences of the United States of America·Stefan WielandFrancis V Chisari
Nov 4, 2004·The Journal of Biological Chemistry·Yulan QingGeorge R Stark
Feb 26, 2005·Journal of Virology·Michael D RobekFrancis V Chisari
Mar 2, 2005·Nature Reviews. Immunology·Barbara Rehermann, Michelina Nascimbeni
May 3, 2005·Nature Reviews. Immunology·Leonidas C Platanias
Aug 9, 2006·Clinical and Vaccine Immunology : CVI·Stephen M RiordanKumar Visvanathan
Sep 29, 2006·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Sean E DoyleKevin M Klucher
Dec 26, 2006·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Kumar VisvanathanStephen Locarnini
May 26, 2007·Nature Reviews. Immunology·Akihiko YoshimuraMasato Kubo
Dec 1, 2007·Nature Reviews. Drug Discovery·Ernest C BordenGeorge R Stark
Oct 25, 2008·Cytokine & Growth Factor Reviews·Julie PiessevauxJan Tavernier
Jan 14, 2009·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Jun WuJoerg F Schlaak
Apr 29, 2009·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Robert Perrillo

❮ Previous
Next ❯

Citations

Mar 8, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hongxiao SongZhengkun Tu
Nov 6, 2018·Viruses·Vanessa Meier-StephensonTrushar R Patel
Apr 17, 2021·Computational and Mathematical Methods in Medicine·Conghui ZhangXinghui Liu

❮ Previous
Next ❯

Methods Mentioned

BETA
nuclear translocation
ELISA
flow cytometry
transfection
PCR

Related Concepts

Related Feeds

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Adrenocortical Carcinoma

Hepatocellular carcinoma is the most common type of primary liver cancer and frequently occurs in individuals with chronic liver diseases like cirrhosis. Here is the latest research.