乙型肝炎病毒e抗原激活细胞因子信号传导抑制因子2以抑制干

StephenW

Sci Rep. 2017 May 11;7(1):1729. doi: 10.1038/s41598-017-01773-6.
Hepatitis B Virus e Antigen Activates the Suppressor of Cytokine Signaling 2 to Repress Interferon Action.
Yu Y1,2, Wan P1, Cao Y1, Zhang W1, Chen J1, Tan L1, Wang Y1, Sun Z1, Zhang Q1, Wan Y1, Zhu Y1, Liu F1, Wu K3, Liu Y4, Wu J5.
Author information

1    State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan, 430071, China.
2    Life Sciences Institute, Zhejiang University, Hangzhou, China.
3    State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan, 430071, China. [email protected].
4    State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan, 430071, China. [email protected].
5    State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan, 430071, China. [email protected].

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.

PMID:
    28496097
DOI:
    10.1038/s41598-017-01773-6

StephenW

Sci Rep。2017 May 11; 7（1）：1729。 doi：10.1038 / s41598-017-01773-6。
乙型肝炎病毒e抗原激活细胞因子信号传导抑制因子2以抑制干扰素作用。
俞Y1 1,2，万P1，曹毅，张W1，陈J Tan，王Y1，孙Z1 Zhang Q1，万Y1，朱Y1，刘F1，吴克3，刘Y 4，吴杰5。
作者信息

1武汉大学病毒学与生命科学学院国家重点实验室，武汉430071。
2浙江大学生命科学学院，杭州，中国。
3武汉大学病毒学与生命科学学院国家重点实验室，武汉430071。 [email protected]。
4武汉大学病毒学与生命科学学院国家重点实验室，武汉430071。 [email protected]。
5武汉大学病毒学与生命科学学院国家重点实验室，武汉430071。 [email protected]。

抽象

乙型肝炎病毒（HBV）感染引起急性乙型肝炎（AHB），慢性乙型肝炎（CHB），肝硬化（LC）和最终肝细胞癌（HCC）。血清中乙型肝炎病毒抗原（HBeAg）的存在通常表示正在进行的病毒复制和疾病进展。然而，HBeAg调控HBV感染的机制仍不清楚。干扰素（IFNs）是参与宿主先天免疫的多效细胞因子。结合受体后，IFN激活JAK / STAT通路刺激IFN刺激的基因（ISG）的表达，导致抗病毒反应的诱导。在这里，我们发现HBeAg抑制IFN / JAK / STAT信号传导以促进HBV复制。最初，HBeAg刺激细胞因子信号传导抑制因子2（SOCS2）的表达。随后，SOCS2通过降低酪氨酸激酶2（TYK2）的稳定性降低IFN / JAK / STAT信号传导，下调I型和III型IFN受体的表达，减弱STAT1的磷酸化和细胞核易位。最后，SOCS2抑制ISG的表达，这导致抑制IFN的作用和促进病毒复制。这些结果证明了HBeAg在调节IFN作用中的重要作用，并提供了一种可能的分子机制，通过该机制，HBV可抵抗IFN治疗并维持持续感染。

结论：
    28496097
DOI：
    10.1038 / s41598-017-01773-6