武汉大学朱应课题组发现TAP1调控抗病毒固有免疫应答新机制

rentianyixu

J Immunol. 2017 Mar 29. pii: 1601588. doi: 10.4049/jimmunol.1601588. [Epub ahead of print]

Inducible TAP1 Negatively Regulates the Antiviral Innate Immune Response by Targeting the TAK1 Complex.

Xia Z1, Xu G1, Yang X1, Peng N1, Zuo Q1, Zhu S1, Hao H1, Liu S1, Zhu Y2.
Author information
1state Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China.
2State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China yingzhu@whu.edu.cn.


Abstract
The innate immune response is critical for host defense and must be tightly controlled, but the molecular mechanisms responsible for its negative regulation are not yet completely understood. In this study, we report that transporter 1, ATP-binding cassette, subfamily B (TAP1), a virus-inducible endoplasmic reticulum-associated protein, negatively regulated the virus-triggered immune response. In this study, we observed upregulated expression of TAP1 following virus infection in human lung epithelial cells (A549), THP-1 monocytes, HeLa cells, and Vero cells. The overexpression of TAP1 enhanced virus replication by inhibiting the virus-triggered activation of NF-κB signaling and the production of IFNs, IFN-stimulated genes, and proinflammatory cytokines. TAP1 depletion had the opposite effect. In response to virus infection, TAP1 interacted with the TGF-β-activated kinase (TAK)1 complex and impaired the phosphorylation of TAK1, subsequently suppressing the phosphorylation of the IκB kinase complex and NF-κB inhibitor α (IκBα) as well as NF-κB nuclear translocation. Our findings collectively suggest that TAP1 plays a novel role in the negative regulation of virus-triggered NF-κB signaling and the innate immune response by targeting the TAK1 complex.

文章链接：http://www.jimmunol.org/content/ ... 88/tab-article-info

rentianyixu

朱应
职称职务：教授、博士生导师、教育部“新世纪人才计划”入选者
专业与研究方向：病毒学及分子病理学
实验室位置：生科院5123室
联系方式：027-68754819 （O）
Email:　yingzhu@whu.edu.cn

学习经历：
2000-2002：美国德州大学医学院，内科系 博士后
1999-2000：美国贝勒医学院，生物化学及分子生物学系 博士后
1995-1998：武汉大学 微生物学 博士
1983-1987：武汉大学 病毒学及分子生物学 学士

工作经历
2014-至今：病毒学系主任
2009-至今：病毒学国家重点实验室，武汉大学“985工程”特聘教授
2007-2010：入选教育部“新世纪人才计划”
2005-2007：获湖北省杰出青年基金资助
2003-至今：武汉大学生命科学学院，教授
1988-1994：武汉大学病毒研究所，助教，讲师

学术兼职
湖北省生物工程学会 常务理事
湖北省生化学会 副理事长
湖北省微生物学会 常务理事
中国微生物学会 会员
美国免疫学会 会员

研究方向与研究兴趣
医学病毒学及分子病理学
　　主要从事人类肝炎病毒，流感病毒感染引起宿主炎症应答的机理。结合临床标本的分析与检测，从转录水平和翻译水平研究病毒感染诱导白介素，干扰素等细胞因子表达调控规律。研究宿主炎症因子网络的形成以及抗病毒免疫应答影响病毒感染的进程。病毒感染诱导环加氧酶（COX-2）及下游炎症反应通路，白介素（IL-27,IL-32），III型干扰素（IFN-lambda）以及氧化氮合成酶（iNOS）的相关信号通路研究。

承担国家科研项目：
2014-2017年，国家自然科学基金中德国际合作项目：
持续性病毒感染中病毒与免疫细胞的相互作用：肝炎病毒感染与免疫应答(81461130019)。

2013-2017年，主持“973计划”课题
重要病毒转录复制蛋白复合体的结构功能研究（2013CB911102）

2013-2017年，主持国家自然科学基金课题面上项目
MVP 在宿主抗病毒天然免疫应答中的作用机制（81271821）

2013-2016年：国家传染病重大专项课题
HBV 细胞和动物模型的建立和应用（2012ZX10004503）

2007-2011年：主持“973计划”课题
乙肝病毒重症化进程中HBV病毒学特点及其致病机制的研究（2007CB512803）

2008-2010年：主持教育部“新世纪优秀人才支持计划”项目
病毒感染与宿主炎症反应网络（NCET-07-0647）

2009-2012年：国家“973计划”课题，
HCV抑制天然免疫反应的机制研究，（2009CB522506）

2010-2012年：主持国家自然科学基金课题，
表观遗传修饰在流感病毒感染炎症网络中的作用 (30979144)

2008-2010年：国家传染病重大专项课题
乙肝病毒感染的细胞模型建立（2008ZX10002-011）

2006-2008年：主持国家自然科学基金面上项目
流感病毒感染诱导炎症因子环加氧酶基因表达的分子机（30570066）

主要学术论文
Liu S, Peng NF, Xie JJ, Hao Q, Zhang M, Zhang Y, Xia ZC, Xu G, Zhao FP, Wang Q, Han T, Zhu Y*, Human hepatitis B virus S and E antigens inhibit major vault protein signaling in interferon induction pathways. Journal of Hepatology 2015, 62. 1015–1023.

Han T, Wan Y, Wang J, Zhao P, Yuan Y, Wang L, She Y, Broering R, Lu M, Ye L, Zhu Y*. Set7 facilitates hepatitis C virus replication via enzymatic activity-dependent attenuation of the IFN-related pathway. J Immunol. 2015, 194(6):2757-68.

Zhao F, Xu G, Zhou Y, Wang L, Xie J, Ren S, Liu S, Zhu Y*. MicroRNA-26b Inhibits Hepatitis B Virus Transcription and Replication by Targeting the Host Factor CHORDC1 Protein. J Biol Chem. 2014, 289(50):35029-41.


Wang J, Wang Q, Han T, Li YK, Zhu SL, Ao F, Feng J, Jing MZ, Wang L, Ye LB and Zhu Y*. Soluble interleukin-6 receptor is elevated during influenza A virus infection and mediates the IL-6 and IL-32 inflammatory cytokine burst Cellular & Molecular Immunology. 2014, 1–12 (In Press)

Li Y, Xie J, Xu X, Wang J, Ao F, Wan Y, Zhu Y*. MicroRNA-548 down-regulates host antiviral response via direct targeting of IFN-λ1. Protein Cell. 2013.4(2):130-41.

Li Y, Xie J, Xu X, Liu L, Wan Y, Liu Y, Zhu C, Zhu Y*. Inducible interleukin 32 (IL-32) exerts extensive antiviral function via selective stimulation of interferon λ1 (IFN-λ1). J Biol Chem. 2013. 288(29):20927-41.

Wang Q, Chen X, Feng J, Cao Y, Song Y, Wang H, Zhu C, Liu S, Zhu Y*.  Soluble interleukin-6 receptor-mediated innate immune response to DNA and RNA viruses. J Virol. 2013. 87(20):11244-54.

Yue X, Wang H, Zhao F, Liu S, Wu J, Ren W, Zhu Y*. Hepatitis B virus-induced calreticulin protein is involved in IFN resistance. J Immunol. 2012;189(1):279-86.

Liu S, Hao Q, Wang Y, Yue X, Peng N, Chen YN, Wu J, Zhu Y*. Major Vault Protein: A Virus-Induced Host Factor against Viral Replication through the Induction of Type-I Interferon. Hepatology. 2012. 56: 57-66.

Liu L, Cao Z, Chen J, Li R, Cao Y, Zhu C, Wu K, Wu J, Liu F, Zhu Y*. Influenza A Virus Induces Interleukin-27 through Cyclooxygenase-2 and Protein Kinase A Signaling. J Biol Chem. 2012 Apr 6;287(15):11899-910.

Fang J, Hao Q, Liu L, Li Y, Wu J, Huo X, Zhu Y*. Epigenetic Changes Mediated by miR29 Activate Cyclooxygenase-2 and Interferon-λ1 Production during Viral Infection. J Virol. 2012. 86(2) 2010-2020.

Li W, Sun W, Liu L, Yang F, Li YK, Chen YN, Fang JL, Zhang WJ, Wu JG, Zhu Y*. Interleukin 32: A Host Proinflammatory Factor against Influenza Viral Replication is Upregulated by Aberrant Epigenetic Modifications during Influenza A Virus Infection. J Immunol. 2010. 185, 5056 -5065.

Li W, Yang F, Liu Y, Gong R, Liu L, Feng Y, Hu P, Sun W, Hao Q, Kang L, Wu J, and Zhu Y*. Negative feedback regulation of IL-32 production by iNOS activation in response to dsRNA or influenza virus infection. Eur. J. Immunol. 2009. 39: 1019-1024.

Rasool ST, Tang H, Wu J, Li W, Mukhtar MM, Zhang J, Mu Y, Xing HX, Wu J, Zhu Y*. Increased level of IL-32 during human immunodeficiency virus infection suppresses HIV replication. Immunol Lett. 2008. 117(2):161-167.

Li W, Liu Y, Mukhtar MM, Gong R, Pan Y, Rasool ST, Gao Y, Kang L, Hao Q, Peng G, Chen Y, Chen X, Wu J, Zhu Y*. Activation of interleukin-32 pro-inflammatory pathway in response to influenza A virus infection. PLoS ONE. 2008 Apr 16;3(4):e1985.

Liu M, Yang Y, Gu C, Yue Y, Wu KK, Wu J, Zhu Y*. Spike protein of SARS-CoV stimulates cyclooxygenase-2 expression via both calcium-dependent and calcium-independent protein kinase C pathways. FASEB J. 2007. 21(7):1586-96.