MxA inhibits hepatitis B virus replication by interaction with hepatitis B core antigen

被引:114
作者
Li, Ning [1 ]
Zhang, Lei [1 ]
Chen, Liangwei [1 ]
Feng, Wenfeng [1 ]
Xu, Yinfeng [1 ]
Chen, Feng [2 ]
Liu, Xiaohong [3 ]
Chen, Zhi [2 ]
Liu, Wei [1 ]
机构
[1] Zhejiang Univ, Sch Med, Program Mol Cell Biol, Dept Biochem & Mol Biol, Hangzhou 310058, Zhejiang, Peoples R China
[2] Zhejiang Univ, Sch Med, Affiliated Hosp 1, State Key Lab Diag & Treatment Infect Dis, Hangzhou 310058, Zhejiang, Peoples R China
[3] Zhejiang Univ, Inst Biotechnol, State Key Lab Rice Biol, Hangzhou 310058, Zhejiang, Peoples R China
关键词
ANTIVIRAL ACTIVITY; TRANSGENIC MICE; PROTEIN; GTPASE; OLIGOMERIZATION; NUCLEOCAPSIDS; AGGRESOMES; RESISTANCE; PROMOTER; DEFENSE;
D O I
10.1002/hep.25608
中图分类号
R57 [消化系及腹部疾病];
学科分类号
100201 [内科学];
摘要
Human MxA, an interferon-inducible cytoplasmic dynamin-like GTPase, possesses antiviral activity against multiple RNA viruses. Recently, MxA has also been demonstrated to have activity against the hepatitis B virus (HBV), a well-known DNA virus responsible for acute and chronic liver disease in humans. We investigated the molecular mechanism for the anti-HBV activity of MxA. Our results demonstrated that in HepG2.2.15 cells, MxA GTPase independently suppressed the production of hepatitis B surface antigen and HBV DNA without changing the level of hepatitis B core antigen (HBcAg) and the distribution of HBV mRNA. MxA significantly reduced the level of the encapsidated pregenomic RNA. Through its central interactive domain, MxA interacted with HBcAg, causing accumulation of the proteins in perinuclear compartments. MxA-HBcAg interaction significantly affected the dynamics of HBcAg by immobilizing HBcAg in the perinuclear structures. Conclusion: MxA displays antiviral activity against HBV involving a mechanism of MxA-HBcAg interaction that may interfere with core particle formation. (HEPATOLOGY 2012;56:803811)
引用
收藏
页码:803 / 811
页数:9
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