STAT1 methylation in the resistance of hep B virus to Interferon alpha

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Antiviral Research
Volume 85, Issue 3, March 2010, Pages 463-469
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doi:10.1016/j.antiviral.2009.10.011 | How to Cite or Link Using DOI
Copyright © 2009 Elsevier B.V. All rights reserved.   

Inhibition of STAT1 methylation is involved in the resistance of hepatitis B
virus to Interferon alpha


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Jie Lia, Feng Chena, Min Zhenga, Haihong Zhua, Dongjiu Zhaoa, Weixia Liua, Wei
Liub and Zhi Chena, ,

a State Key Laboratory of Infectious Disease Diagnosis and Treatment, First
Affiliated Hospital, Zhejiang University College of Medicine, 79 Qingchun
Road, Hangzhou, Zhejiang 310003, China
b Department of Biochemistry, Zhejiang University College of Medicine, 388
Yu-Hang Tang Road, Hangzhou, Zhejiang 310058, China

Received 30 June 2009;  revised 11 October 2009;  accepted 16 October 2009.
Available online 24 October 2009.

Abstract
As a major therapy for hepatitis B virus (HBV) infection, Interferon alpha
(IFN-alpha) triggers intracellular signal transduction including JAK-STAT
pathway to produce various antiviral effector mechanisms. However, patients
with chronic hepatitis B usually show low response to IFN-alpha treatment and
the underlying mechanism remains unclear. In the present study, HepG2 and
HepG2.2.15 cells were used to examine the Type I IFN receptors expression,
phosphorylation and methylation of STAT1. STAT1–PIAS1 interaction in cells
was tested by protein co-immunoprecipitation. The potential improvement of
S-adenosylmethionine (SAM) in the antiviral effect of IFN-alpha was also
investigated. Our data demonstrated that both chains of the Type I IFN
receptors were expressed for a much higher extent in HepG2.2.15 cells than in
HepG2 cells. HBV inhibited dramatically the methylation rather than the
phosphorylation of STAT1, which was consistent with an increased STAT1–PIAS1
interaction. Combined with IFN-alpha, SAM treatment effectively improved STAT1
methylation and attenuated STAT1–PIAS1 binding, followed by increased PKR
and 2′,5′-OAS mRNA expression, thus significantly reducing the HBsAg,
HBeAg protein levels and HBV DNA load in the supernatant of HepG2.2.15 cells.
Less STAT1 methylation and subsequent increased STAT1–PIAS1 interaction are
involved in the mechanism of the IFN-alpha-antagonistic activity of HBV. By
improving STAT1 methylation, SAM can enhance the antiviral effect of IFN-alpha.

富贵数字

看不懂

走遍四方

确实深奥，完全学术探讨，MS没有比较实质的东西在此篇论文。
继续。。。

lemonades

有实在的东西，仔细看。跟耐药有关。
跟我无关，所以我没仔细看。