[Technical]Hepatitis B Virus Regulatory HBx Protein Binds to Adaptor Protein IPS

StephenW

These results demonstrate that HBx interferes with the RIG-I
pathway of innate immunity. Hepatitis B virus now joins hepatitis C virus and
hepatitis A virus in targeting the same innate immune response pathway,
presumably as a shared strategy to benefit replication of these viruses in the
liver.
这些结果表明，HBx干扰RIG-I先天免疫途径。乙型肝炎现在加入丙型肝炎和A型肝炎, 针对相同的先天免疫反应途径的病毒，这应该是共同的战略,利益这些病毒在肝脏的复制。


<http://jvi.asm.org/cgi/content/abstract/85/2/987>


Journal of Virology, January 2011, p. 987-995, Vol. 85, No. 2
0022-538X/11/$012.00+0     doi:10.1128/JVI.01825-10
Copyright © 2011, American Society for Microbiology. All Rights Reserved.

Hepatitis B Virus Regulatory HBx Protein Binds to Adaptor Protein IPS-1 and
Inhibits the Activation of Beta Interferon

Manish Kumar,1, Sung Yun Jung,2, Amanda J. Hodgson,1 Charles R. Madden,1, Jun
Qin,2 and Betty L. Slagle1*

Departments of Molecular Virology and Microbiology,1 Verna and Marrs McLean
Department of Biochemistry and Molecular Biology, Baylor College of Medicine,
Houston, Texas 770302

Received 27 August 2010/ Accepted 3 November 2010


Hepatitis B virus (HBV) encodes the regulatory HBx protein, which is required
for virus replication, although its specific role(s) in the replication cycle
remains under investigation. An immunoprecipitation/mass spectrometry approach
was used to identify four novel HBx binding proteins from the cytoplasmic
fraction of HBx transgenic mouse livers. One of these HBx binding partners is
beta interferon promoter stimulator 1 (IPS-1), an adaptor protein that plays a
critical role in mediating retinoic acid-inducible gene I (RIG-I) signaling,
which leads to the activation of beta interferon (IFN-β). The HBx-IPS-1 protein
interaction was confirmed in plasmid-transfected HepG2 cells by reciprocal
coimmunoprecipitation and Western blotting. We hypothesized that HBx might alter
IPS-1 function since proteins of hepatitis C virus and hepatitis A virus
similarly bind IPS-1 and target it for inactivation. The effect of HBx on
IPS-1-mediated IFN-β signaling was tested in transfected 293T and HepG2 cells,
and we show that HBx inhibits double-stranded DNA (dsDNA)-mediated IFN-β
activation in a dose-dependent manner when expressed either alone or within the
context of HBV replication. However, HBx does not inhibit poly(I:C)-activated
IFN-β signaling. These results demonstrate that HBx interferes with the RIG-I
pathway of innate immunity. Hepatitis B virus now joins hepatitis C virus and
hepatitis A virus in targeting the same innate immune response pathway,
presumably as a shared strategy to benefit replication of these viruses in the
liver.

--------------------------------------------------------------------------------
* Corresponding author. Mailing address: One Baylor Plaza, MS-385, Houston, TX
77030. Phone: (713) 798-3006. Fax: (713) 798-5075. E-mail: [email protected]  
Published ahead of print on 10 November 2010.  M.K. and S.Y.J. contributed
equally to this report.  Present address: Department of Biology, George Mason
University, Fairfax, VA.



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MP4

看来RIG-I是个关键点.

StephenW

MP4 发表于 2011-1-11 22:00
看来RIG-I是个关键点.

我对RIG-I没有知识.我记得你曾经说过HBVer的免疫系统被破坏.现在我多明白这一点了。
在我看来，乙肝表面抗原和监管HBx蛋白,两个都可能干扰HBVer的免疫系统, "利益这些病毒在肝脏的复制".如果我们能减少肝表面抗原和监管HBx蛋白的数量, 可能可以帮助我们的免疫系统来杀死病毒.
这是我的愚见.

flashwq

RIG-I 其实是一个能识别很多RNA病毒的receptor,并不是对HBV特异性,其实这个家族还有其它好几个receptor蛋白,

StephenW

回复 flashwq 的帖子

I am sure you are right. I don't understand the article fully, far from it. But it is interesting to know that HBx interferes with the RIG-I pathway. Maybe you can explain to us the full significance of the RIG-I pathway of immunity.