个人简历

中山大学中山医学院人类病毒学研究所教授，病毒性肝炎研究组负责人。2004年获得中国农业大学生物学院生物化学与分子生物学（分子病毒学研究方向）博士学位，博士学习期间到丹麦皇家兽医研究所（现丹麦技术大学国家兽医研究所）和德国Friedrich-Loeffler研究所学习一年。2004和2006-2007年间，在丹麦技术大学国家兽医研究所分别做项目研究员(Project Researcher)和博士后。2005年，到加拿大萨斯喀彻温大学疫苗与传染病研究所做博士后，开始从事丙型肝炎病毒（hepatitis C virus, HCV）研究；2008-2014年1月，在丹麦哥本哈根大学Hvidovre医院传染病与临床研究中心和医学与健康科学学院CO-HEP研究组继续HCV的研究，任博士后和资深研究员（Senior Investigator）。2014年1月，获中山大学“百人计划二期”和广东省“引进创新科研团队项目”子项目启动经费支持，全职回中山大学中山医学院工作。

研究领域

长期从事病毒学研究工作，特别是在HCV的分子生物学、细胞感染模型和抗病毒药物的研究上，取得系列重要研究成果。探索出一套系统的新方法，鉴定出一组关键突变，建立了新型全长HCV基因1a型TNcc克隆，2a型J6cc克隆和2b型J8cc克隆等，并证明这些感染性HCV克隆对主要临床抗病毒药物反应的浓度依赖性和基因型特异性。这些成果开辟了建立HCV细胞感染模型的新途径。此外，还建立了基于JFH1的基因1-6型5’UTR-NS2和5’UTR-NS5A的嵌合体细胞感染模型，并证明HCV 5’UTR茎环结构I（SLI）的功能对基因1-6型病毒的必须性。证明HCV基因1-6型的感染对宿主微小RNA（microRNA）miR-122的依赖性；发现宿主细胞RNA和HCV本身基因序列有功能的插入到HCV 5’UTR SLI，并降低miR-122沉默对HCV感染的抑制效果，指出以miR-122为靶点的单方治疗可能遇到病毒逃逸的机理。

近期论文

Chen M, Zheng F，Yuan G, Duan X, Rong L, Liu J, Feng S, Wang Z, Wang M, Feng Y, Zhou Q, Li J, Deng K, Li C, Xia J, Rao G, Zhou Y, Fu Y, Li YP*. Development of an infectious cell culture system for hepatitis C virus genotype 6a clinical isolate using a novel strategy and its sensitivity to direct-acting antivirals. Frontiers in Microbiology 2018; Accepted (in press). Wang Y, Chen X, Xie J, Zhou S, Huang Y, Li YP, Li X, Liu C, He J*, Zhang P*. RNA helicase A is an important host factor involved in dengue virus replication. Journal of Virology 2018; Accepted (in press). Zheng Y#, Liu Q#, Wu Y#, Ma L, Zhang Z, Liu T, Jin S, She Y, Li YP*, Cui J*. Zika virus elicits inflammation to evade antiviral response by cleaving cGAS via NS1-caspase-1 axis. The EMBO Journal 2018;37(18). pii: e99347. PMID: 30065070 (PubMed) Chen Y, Liu T, Zhang Z, Chen M, Rong L, Ma L, Yu B, Wu, Zhang P, Zhu X, Huang X, Zhang H, Li YP*. Novel genetically stable infectious clone for a Zika virus clinical isolate and identification of RNA elements essential for virus production. Virus Research. 2018;257:14-24. PMID: 30144463 (PubMed) Duan X, Anwar MI, Xu Z, Ma L, Yuan G, Chen Y, Liu X, Xia J, Zhou Y, Li YP*. Adaptive Mutation F772S-enhanced p7-NS4A Cooperation Facilitated the Assembly and Release of Hepatitis C Virus and Associated with Enlargement of Lipid Droplets. Emerging Microbes & Infections 2018 Aug 8;7(1):143. PMID: 30087320 (PubMed) Humes D, Ramirez S, Jensen TB, Li YP, Gottwein JM, Bukh J*. Recombinant hepatitis C virus genotype 5a infectious cell culture systems expressing minimal JFH1 NS5B sequences permit polymerase inhibitor studies. Virology 2018;522:177-192. PMID: 30032031 (PubMed) Li J, Feng S, Liu X, Guo M, Chen M, Chen Y, Rong L, Xia J, Zhou Y, Zhong J, Li YP*. Identification of nucleotides in the 5'UTR and amino acids substitutions that are essential for the infectivity of 5'UTR-NS5A recombinant of hepatitis C virus genotype 1b (strain Con1). Virology 2018;518:253-263. PMID: 29549787 (PubMed) Yang JY, Deng XY, Li YS, Ma XC, Feng JX, Yu B, Chen Y, Luo YL, Wang X, Chen ML, Fang ZX, Zheng FX, Li YP, Zhong Q, Kang TB, Song LB, Xu RH, Zeng MS, Chen W, Zhang H, Xie W, Gao S*. Structure of Schlafen13 reveals a new class of tRNA/rRNA- targeting RNase engaged in translational control. Nature Communications 2018;9(1):1165. PMID: 29563550 (PubMed) Pham LV, Ramirez S, Gottwein JM, Fahnøe U, Li YP, Pedersen J, Bukh J*. HCV Genotype 6a Escape from and Resistance to Velpatasvir, Pibrentasvir, and Sofosbuvir in Robust Infectious Cell Culture Models. Gastroenterology 2018154(8):2194-2208.e12. PMID: 29454794 (PubMed) Hu L, Li J, Cai H, Yao W, Xiao J, Li YP, Qiu X, Xia H, Peng T*. Avasimibe: A novel hepatitis C virus inhibitor that targets the assembly of infectious viral particles. Antiviral Research 2017;148:5-14. PMID: 29074218 (PubMed) Huang LH, Xu MY, Li HJ, Li JQ, Chen YX, Ma WZ, Li YP, Xu J*, Yang DP*, Lan WJ*. Amino Acid-Directed Strategy for Inducing the Marine-Derived Fungus Scedosporium apiospermum F41−1 to Maximize Alkaloid Diversity. Organic Letters 2017;19:4888-4891. PMID:28837349 (PubMed) Yuan G, Liu J, Hu C, Huang H, Qi M, Wu T, Liang W, Li YP, Zhang YY, Zhou Y*. Genotype Distribution and Molecular Epidemiology of Hepatitis C Virus in Guangzhou, China: Predominance of Genotype 1b and Increasing Incidence of Genotype 6a. Cellular Physiology and Biochemistry 2017;43(2):775-787. PMID:28950254 (PubMed) Yin P, Zhang L, Ye F, Deng Y, Lu S, Li YP, Zhang L, Tan W*. A screen for inhibitory peptides of hepatitis C virus identifies a novel entry inhibitor targeting E1 and E2. Scientific Reports 2017;7(1):3976. PMID: 28638089 (PubMed) Fang S, Su J, Liang B, Li X, Li Y, Jiang J, Huang J, Zhou B, Ning C, Li J, Ho W, Li YP, Chen H, Liang H, Ye L*. Suppression of autophagy by mycophenolic acid contributes to inhibition of HCV replication in human hepatoma cells. Scientific Reports 2017;7:44039. PMID:28276509 (PubMed) Li X, Li Y, Fang S, Su J, Jiang J, Liang B, Huang J, Zhou B, Zang N, Ho W, Li J, Li YP, Chen H, Ye L, Liang H*. Downregulation of autophagy-related gene ATG5 and GABARAP expression by IFN-λ1 contributes to its anti-HCV activity in human hepatoma cells. Antiviral Research 2017;140:83-94. PMID:28131804 (PubMed) Pham LV, Ramirez S, Carlsen TH, Li YP, Gottwein JM, Bukh J*. Efficient hepatitis C virus genotype 1b Core-NS5A recombinants permit efficacy testing of protease and NS5A inhibitors. Antimicrobial Agents and Chemotherapy 2017 24;61(6). pii: e00037-17, PMID:28348150 (PubMed) Chi X, Niu Y, Cheng M, Liu X, Feng Y, Zheng F, Fan J, Li X, Jin Q, Zhong J, Li YP, Yang W*. Identification of a Potent and Broad-Spectrum Hepatitis C Virus Fusion Inhibitory Peptide from the E2 Stem Domain. Scientific Reports 2016;6:25224. PMID:27121372 (PubMed) Serre SB, Jensen SB, Ghanem L, Humes DG, Ramirez S, Li YP, Krarup H, Bukh J, Gottwein JM*. Hepatitis C Virus Genotype 1 to 6 Protease Inhibitor Escape Variants: In Vitro Selection, Fitness, and Resistance Patterns in the Context of the Infectious Viral Life Cycle. Antimicrobial Agents and Chemotherapy 2016;60(6):3563-78. PMID:27021330 (PubMed) Li YP#, Van Pham L#, Uzcategui N, Bukh J. Functional analysis of microRNA-122 binding sequences of hepatitis C virus and identification of variants with high resistance against a specific antagomir. Journal of General Virology 2016;97(6):1381-94. PMID:26935756 (PubMed) Jensen SB, Serre SB, Humes DG, Ramirez S, Li YP, Bukh J, Gottwein JM*. Substitutions at NS3 Residue 155, 156, or 168 of Hepatitis C Virus Genotypes 2 to 6 Induce Complex Patterns of Protease Inhibitor Resistance. Antimicrobial Agents and Chemotherapy 2015;59(12):7426-36. PMID:26392503 (PubMed)