Hepatitis B Virus e antigen activates the suppressor of cytokine signaling 2 to repress interferon action

Yi Yu, Pin Wan, Yanhua Cao, Wei Zhang, Junbo Chen, Li Tan, Yan Wang, Zhichen Sun, Qi Zhang, Yushun Wan, Ying Zhu, Fang Liu, Kailang Wu, Yingle Liu, Jianguo Wu

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17 Scopus citations


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 regulation of IFN action, and provide a possible molecular mechanism by which HBV resists the IFN therapy and maintains persistent infection.

Original languageEnglish (US)
Article number1729
JournalScientific reports
Issue number1
StatePublished - Dec 1 2017
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by research grants from the Major State Basic Research Development Program (973 Program), Ministry of Science and Technology of the Peoples Republic of China (2012CB518900), the National Natural Science Foundation of China (31230005, 81471942, 31270206, 31200134, and 81171525), the National Mega Project on Major Infectious Disease Prevention, National Health and Family Planning Commission of China (2012ZX10002006-003 and 2012ZX10004-207), and the Chinese Foundation for Hepatitis Prevention and Control (grant number CFHPC20132153).

Publisher Copyright:
© 2017 The Author(s).


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