Hepatitis B Virus e Antigen Activates the Suppressor of Cytokine Signaling 2 to Repress Interferon Action
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....
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Nature Portfolio
2017
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oai:doaj.org-article:1c5c73e8fb33400aa8066a4f4cb1d1222021-12-02T11:52:34ZHepatitis B Virus e Antigen Activates the Suppressor of Cytokine Signaling 2 to Repress Interferon Action10.1038/s41598-017-01773-62045-2322https://doaj.org/article/1c5c73e8fb33400aa8066a4f4cb1d1222017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01773-6https://doaj.org/toc/2045-2322Abstract 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.Yi YuPin WanYanhua CaoWei ZhangJunbo ChenLi TanYan WangZhichen SunQi ZhangYushun WanYing ZhuFang LiuKailang WuYingle LiuJianguo WuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017) |
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Medicine R Science Q |
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Medicine R Science Q 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 Hepatitis B Virus e Antigen Activates the Suppressor of Cytokine Signaling 2 to Repress Interferon Action |
| description |
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 regulation of IFN action, and provide a possible molecular mechanism by which HBV resists the IFN therapy and maintains persistent infection. |
| format |
article |
| author |
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 |
| author_facet |
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 |
| author_sort |
Yi Yu |
| title |
Hepatitis B Virus e Antigen Activates the Suppressor of Cytokine Signaling 2 to Repress Interferon Action |
| title_short |
Hepatitis B Virus e Antigen Activates the Suppressor of Cytokine Signaling 2 to Repress Interferon Action |
| title_full |
Hepatitis B Virus e Antigen Activates the Suppressor of Cytokine Signaling 2 to Repress Interferon Action |
| title_fullStr |
Hepatitis B Virus e Antigen Activates the Suppressor of Cytokine Signaling 2 to Repress Interferon Action |
| title_full_unstemmed |
Hepatitis B Virus e Antigen Activates the Suppressor of Cytokine Signaling 2 to Repress Interferon Action |
| title_sort |
hepatitis b virus e antigen activates the suppressor of cytokine signaling 2 to repress interferon action |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/1c5c73e8fb33400aa8066a4f4cb1d122 |
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