感染机制组

(一)本组简介

病毒、宿主间相互作用机制与靶点研究课题组的主要研究对象是戊型肝炎病毒(HEV)及呼吸道合胞病毒(RSV),主要研究方向是通过研究病毒的感染及宿主免疫机制发现可以用于针对、预防与治疗的靶点。

HEV研究方向主要从HEV衣壳关键domain入手,发现高亲和力表位、宿主结合表位及广谱中和表位,并将发现的靶点及其作用机制运用到高灵敏度诊断试剂的研发、病毒跨宿主传播机制、以及疫苗作用机制的阐述中。基于小组的研究成果已成功开发出新一代HEV抗原高灵敏度诊断试剂,并确定该试剂在戊型肝炎的检测及确诊中起到重要作用。同时该小组的研究还解释了HEV跨物种传播的潜在氨基酸变异及感染入胞的潜在途径,并发现了抗HEV抗体应答的潜在靶点。

RSV研究方向与美国国立卫生研究院下属疫苗研究中心(Vaccine Research Center,NIAID,NIH)在RSV领域展开合作,鉴定出了一株高效中和单抗能够稳固RSV融合蛋白F的瞬时构象,并发现了位于该构象上的强中和靶点,该表位已被成功运用到疫苗设计中,其系列研究成果作为疫苗领域的重要突破入选了《Science》杂志2013年度十大科技进展;同时该新发现抗体的体外中和活性比已上市的抗RSV抗体药物高50-100倍,具有很好的应用前景。最近,该小组也筛选到了有望替代5C4的新一代广谱高效中和抗体药物,目前正在积极开展临床前相关实验,展现了良好的临床转化潜能;同时该组研发的RSV灭活疫苗也正在进行临床前的验证阶段,有望成为未来新一代安全有效的RSV灭活疫苗;此外,该小组成员也对RSV胞间传播机制阐述进行了深入的研究,提出了RSV胞间传播新假说,为RSV的防治提供了新的科学依据和理论指导。

(二)导师

郑子峥

(三)正在开展的项目

序号     研究项目                           合作单位

1        不同基因HEV的宿主范围不同的感染机制    

2        HEV疫苗保护性机制研究              美国Scripps研究所

3        血站献血人群HEV流行情况及HEV抗原诊断试剂在临床研究中应用价值  

4        HEV不同病毒形态及生活史研究        UC Davids

5        HEV受体研究  

6        HEV疫苗免疫后人群抗体演化分析

7        RSV疫苗研究  

8        RSV病毒感染机制研究

9        RSV高中和抗体筛选及F高中和表位研究    

10       RSV作为溶瘤病毒进行肿瘤治疗研究

(四)近5年来发表的部分文章

Xin Yin, Dong Ying, Sébastien Lhomme, Zimin Tang, Christopher M. Walker, Ningshao Xia, Zizheng Zhengb,and Zongdi Feng. Origin, antigenicity, and function of a secreted form of ORF2 in hepatitis E virus infection. PNAS,2018,115(8):4773-4778.

Chenguang Shen#, Junyu Chen#, Rui Li#, Mengya Zhang#, Guosong Wang#, Jing Chen, Jianli Cao, Limin Zhang, Xingjian Bi, Hai Yu, Kunyu Yang, Stephen F. Anderson, Timothy Alefantis, Shaojun Ke, Yanbin Wu, Qiangyuan Han, Qingbing Zheng, Mujing Fang, Wenxin Luo, Zizheng Zheng, Quan Yuan, Jun Zhang, J. Wai-Kuo Shih, Harold Kleanthous, Honglin Chen, Yixin Chen*, Ningshao Xia*. A novel multimechanistic antibody targeting receptor-binding sites potently cross-protects against influenza B viruses since 1940. Sci Transl Med. 2017, 18;9(412).

Daiyin Tian#,Michael B. Battles#, Syed M. Moin, Man Chen, Kayvon Modjarrad, Azad Kumar,Masaru Kanekiyo, Kevin W. Graepel, Noor M. Taher, Anne L. Hotard, Martin L. Moore, Min Zhao,Zi-Zheng Zheng,,Ning-Shao Xia*, Jason S. McLellan*& Barney S. Graham*. Structural basis of respiratory syncytial virus subtype-dependent neutralization by an antibody targeting the fusion glycoprotein. Nat Commun. 2017; 8: 1877.

Gui-Ping Wen, Zi-Min Tang, Si-Ling Wang, Wen-Fang Ji, Wei Cai, Xu Zhang, Shou-Jie Huang, Ting Wu, Jun Zhang, Zi-Zheng Zheng*, Ning-Shao Xia*. Classification of human and zoonotic group hepatitis E virus (HEV) using antigen detection. Appl Microbiol Biotechnol. 2017;101(23-24):8585-8594.

Zimin Tang, Siling Wang, Ying Dong, Guiping Wen, Wei Cai, Ke Zhang, Wenfang Ji, Ming Yang, Zizheng Zheng*, Ningshao Xia*. The Bama miniature swine is susceptible to experimental HEV infection. Scientific reports. 2016, 18;6:31813.

Wei Cai, Zimin Tang, Guiping Wen, Siling Wang, Wenfang Ji, Ming Yang, Ying Dong, Zizheng Zheng*, Ningshao Xia*. A high-throughput neutralizing assay for antibodies and sera against hepatitis E virus. Scientific reports. 2016, 28;6:25141.

Min Zhao, Xiao-Jing Li, Zi-Min Tang, Fan Yang,Si-Ling Wang, Wei Cai, Ke Zhang, Zi-Zheng Zheng* and Ning-Shao Xia*. A Comprehensive Study of Neutralizing Antigenic Sites on the Hepatitis E Virus (HEV) Capsid by Constructing, Clustering, and Characterizing a Tool Box. J Bio Chem, 2015.

Wen GP, Tang ZM, Yang F, Zhang K, Ji WF, Cai W, Huang SJ, Wu T, Zhang J, Zheng ZZ*, Xia NS*. A valuable antigen detection method for the diagnosis of acute hepatitis E. J Clin Microbiol, 2015. ?

Zi-Min Tang, Ming Tang, Min Zhao, Gui-Ping Wen, Fan Yang, Wei Cai, Si-Ling Wang, Zi-Zheng Zheng*, Ning-Shao Xia*. A novel linear neutralizing epitope of hepatitis E virus. Vaccine, 2015.

McLellan JS, Chen M, Joyce MG, Sastry M, Stewart-Jones GB, Yang Y, Zhang B, Chen L, Srivatsan S, Zheng A, Zhou T, Graepel KW, Kumar A, Moin S, Boyington JC, Chuang GY, Soto C, Baxa U, Bakker AQ, Spits H, Beaumont T, Zheng Z, Xia N, Ko SY, Todd JP, Rao S, Graham BS, Kwong PD. Structure-based design of a fusion glycoprotein vaccine for respiratory syncytial virus. Science, 2013

McLellan JS, Chen M, Leung S, Graepel KW, Du X, Yang Y, Zhou T, Baxa U, Yasuda E, Beaumont T, Kumar A, Modjarrad K, Zheng Z, Zhao M, Xia N, Kwong PD, Graham BS. Structure of RSV fusion glycoprotein trimer bound to a prefusion-specific neutralizing antibody. Science, 2013

Xu J, Wu F, Tian D, Wang J, Zheng Z, Xia N. Open reading frame 3 of genotype 1 hepatitis E virus inhibits nuclear factor-κappa B signaling induced by tumor necrosis factor-α in human A549 lung epithelial cells. PLOS ONE, 2014

Wei MX, Zhang X, Yu H, Tang ZM, Wang KH, Li ZY, Zheng ZZ, Li SW, Zhang J, Xia NS*, Zhao QJ*. Bacteria expressed hepatitis E virus capsid proteins maintain virion-like epitopes. Vaccine. 2014

Zhang P, Chen Y, Zeng Y, Shen C, Li R, Guo Z, Li S, Zheng Q, Chu C, Wang Z, Zheng Z, Tian R, Ge S, Zhang X, Xia NS, Liu G, Chen X. Virus-mimetic nanovesicles as a versatile antigen-delivery system. PNAS, 2015

Zheng ZZ, Sun YY, Zhao M, Huang H, Zhang J, Xia NS, Miao J, Zhao Q. Specific interaction between hnRNP H and HPV16 L1 proteins: implications for late gene auto-regulation enabling rapid viral capsid protein production. Biochem Biophys Res Commun, 2013.

(五)招生要求

本科期间主修生命科学及医学有关专业,接触过生化、细胞或免疫学等基础实验,热爱科研。为人积极主动,谦虚好学,思维活跃,具有良好的沟通能力和学习能力。性格活泼开朗,兴趣广泛,吃苦耐劳,可以承受实验室较大的工作强度和压力。


国家传染病诊断试剂与疫苗工程技术研究中心(厦门大学)  地址:中国福建省厦门市翔安区翔安南路厦门大学翔安校区
电话:0592-2183111 传真:0592-2181258  邮编:361102
ICP备案号:D200327