Accepted Manuscript
MDA5 Plays a Critical Role in Interferon Respon during Hepatitis C Virus
Infection
Xuezhi Cao, Qiang Ding, Jie Lu, Wanyin Tao, Bing Huang, Yanan Zhao, Junqi
Niu, Yong-Jun Liu, Jin Zhong
PII:S0168-8278(14)00850-2
DOI:/10.1016/j.jhep.2014.11.007
Reference:JHEPAT 5426
To appear in:Journal of Hepatology
Received Date:7 July 2014
Revid Date: 5 November 2014
Accepted Date:7 November 2014
Plea cite this article as: Cao, X., Ding, Q., Lu, J., Tao, W., Huang, B., Zhao, Y., Niu, J., Liu, Y-J., Zhong, J., MDA5 Plays a Critical Role in Interferon Respon during Hepatitis C Virus Infection, Journal of Hepatology (2014), doi: /10.1016/j.jhep.2014.11.007
This is a PDF file of an unedited manuscript that has been accepted for publication. As a rvice to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typetting, and review of the resulting proof before it is published in its final form. Plea note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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MDA5 Plays a Critical Role in Interferon Respon during Hepatitis C Virus Infection 2
Short title: MDA5 ns HCV infection to induce IFN respon
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Xuezhi Cao a,1, Qiang Ding a,1, Jie Lu a, Wanyin Tao a, Bing Huang a, Yanan Zhao a, Junqi Niu a,b, 5
Yong-Jun Liu a,c, and Jin Zhong a,2
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a Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai,
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Shanghai Institutes for Biological Sciences, Chine Academy of Sciences, Shanghai, 200031, China;
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b Department of Hepatology, First Hospital of Jilin University, Changchun, Jilin, 130021,
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China,
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c Baylor Institute for Immunology Rearch, 3434 Live Oak, Dallas, TX 75204, USA.
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1X.C. and Q.D. contributed equally to this work.
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2Corresponding author: Institut Pasteur of Shanghai, Chine Academy of Sciences, 320
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Y ueyang Road, Shanghai, 200031, China. Phone: (86) 21-54923143. Fax: (86) 21-54923142.
E-mail: jzhong@
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Word counts: 5972 words
Number of figures and t ables: 7 Figures
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List of abbreviations:
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HCV: Hepatitis C Virus
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RIG-I: Retinoic Acid Inducible Gene
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MDA5: Melanoma Differentiation-Associated Protein
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IFN: Interferon
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UTR: Untranslated Region
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MAVS: Mitochondrial Antiviral Signaling Protein
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PAMP: Pathogen-associated Molecular Patterns
HCVcc: HCV cell culture
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Conflict of interest: We d eclare that we have no conflict of interest.
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Financial support: This work was supported by grants from National Natural Science 14
Foundation of China (81330039), Chine National Science and Technology Major Project 15
(2012ZX10002007-003), the CAS/SAFEA International Partnership Program for Creative 16
Rearch Teams, Shanghai Pasteur Health Rearch Foundation (SPHRF2013002).
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Author contributions: X.C., Q.D., J.Z. contributed to study design, X.C., Q.D., J.L., W.T.,
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观沧海翻译
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B.H., Y.Z. contributed to data acquisition and analysis, Q.D., X.
C., J.Z. contributed to
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manuscript writing, and J.Z., J.N., Y.L. contributed to study supervision and obtaining funding.
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ABSTRACT (243 Words)
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Background and aims: Hepatitis C virus (HCV) is a human pathogen that can evade host
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immunity to cau persistent infection, leading to liver cirrhosis and hepatocellular carcinoma.
the descendants
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The transfected 3’UTR of HCV genomic RNA can be recognized by host protein RIG-I to
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activate interferon production in hepatocytes. However, it is difficult to demonstrate the
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RIG-I mediated nsing of HCV genomic RNA in the context of HCV infection becau
HCV encoded-NS3-4A protea can inactivate MA VS, a critical adaptor protein in interferon 7thirsty是什么意思
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signaling. Our aim was to identify the viral nsor that triggers interferon respon in
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hepatocytes during HCV infection.
Methods: We generated a hepatic cell line that stably express mutant MA VS resistant to the
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NS3-4A cleavage. This cell line allowed us to investigate interferon signaling pathway in the
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context of HCV infection. By using the knockdown and knockout technology together with
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cucumberbiochemical approaches, we were able to identify the actual viral nsor in hepatocytes
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during HCV infection.
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Results:We showed that HCV infection induced robust interferon respon in the cells
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expressing MAVS resistant to the NS3-4A cleavage. Unexpectedly, the interaction between
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HCV’s 3’UTR and RIG-I emed to play a minor role in this activation, while anotherance
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大专生出国留学条件helica MDA5 played a more important role in nsing HCV infection to trigger interferon
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respon.
Conclusions:Our data demonstrate that MDA5 recognizes HCV to initiate host innate
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immune respon during HCV infection. This study provides insight into how host ns
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HCV to initiate innate immunity during HCV infection. 2
Keywords: HCV, MDA-5, Interferon, Innate Immunity 3
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