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学科主题基础医学
Composition and Interactions of Hepatitis B Virus Quasispecies Defined the Virological Response During Telbivudine Therapy
Zhou, Bin1; Dong, Hui2; He, Yungang3; Sun, Jian1; Jin, Weirong2,4; Xie, Qing5; Fan, Rong1; Wang, Minxian3; Li, Ran3; Chen, Yangyi2; Xie, Shaoqing4; Shen, Yan4; Huang, Xin3; Wang, Shengyue2; Lu, Fengming6; Jia, Jidong7; Zhuang, Hui6; Locarnini, Stephen8; Zhao, Guo-Ping2,3,9,10,11,12,13; Jin, Li3,10,11,12,13; Hou, Jinlin1,14
刊名SCIENTIFIC REPORTS
2015-11-24
DOI10.1038/srep17123
5
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Multidisciplinary Sciences
研究领域[WOS]Science & Technology - Other Topics
关键词[WOS]NAIVE PATIENTS ; DRUG-RESISTANCE ; MUTANTS
英文摘要

Reverse transcriptase (RT) mutations contribute to hepatitis B virus resistance during antiviral therapy with nucleos(t)ide analogs. However, the composition of the RT quasispecies and their interactions during antiviral treatment have not yet been thoroughly defined. In this report, 10 patients from each of 3 different virological response groups, i.e., complete virological response, partial virological response and virological breakthrough, were selected from a multicenter trial of Telbivudine treatment. Variations in the drug resistance-related critical RT regions in 107 serial serum samples from the 30 patients were examined by ultra-deep sequencing. A total of 496,577 sequence reads were obtained, with an average sequencing coverage of 4,641X per sample. The phylogenies of the quasispecies revealed the independent origins of two critical quasispecies, i.e., the rtA181T and rtM204I mutants. Data analyses and theoretical modeling showed a cooperative-competitive interplay among the quasispecies. In particular, rtM204I mutants compete against other quasispecies, which eventually leads to virological breakthrough. However, in the absence of rtM204I mutants, synergistic growth of the drug-resistant rtA181T mutants with the wild-type quasispecies could drive

语种英语
WOS记录号WOS:000365198100002
项目编号2012ZX10002003 ; 2013ZX10004104-002 ; 12ZR1421200 ; 91331107 ; 91331109 ; 31171279
资助机构National Science and Technology Major Project ; key Clinical Specialty Discipline Construction Program, Shanghai Commission for Science and Technology ; National Natural Science Foundation of China
引用统计
被引频次:6[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/62926
专题北京大学基础医学院
作者单位1.Southern Med Univ, Nanfang Hosp, Dept Infect Dis, Guangdong Prov Key Lab Viral Hepatitis Res,State, Guangzhou, Peoples R China
2.Chinese Natl Human Genome Ctr, Shanghai MOST Key Lab Hlth & Dis Gen, Shanghai, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Plant Physiol & Ecol,CAS Key Lab Computation, CAS Key Lab Synthet Biol,CAS MPG Partner Inst Com, Shanghai, Peoples R China
4.Shanghai Shenyou Biotechnol Co Ltd, Shanghai, Peoples R China
5.Victorian Infect Dis Reference Lab, Victoria, Australia
6.Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Dept Infect Dis, Shanghai 200030, Peoples R China
7.Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Ctr Infect Dis,Dept Microbiol, Beijing 100871, Peoples R China
8.Capital Med Univ, Beijing Friendship Hosp, Liver Res Ctr, Beijing, Peoples R China
9.Chinese Univ Hong Kong, Prince Wales Hosp, Li Ka Shing Inst Hlth Sci, Dept Microbiol, Hong Kong, Hong Kong, Peoples R China
10.Fudan Univ, State Key Lab Genet Engn, Shanghai 200433, Peoples R China
11.Fudan Univ, Minist Educ, Key Lab Contemporary Anthropol, Sch Life Sci, Shanghai 200433, Peoples R China
12.Fudan Univ, Inst Biomed Sci, Key Lab Med Mol Virol, Ministries Educ & Hlth,Shanghai Med Coll, Shanghai 200433, Peoples R China
13.Fudan Univ, Dept Microbiol, Sch Life Sci, Shanghai 200433, Peoples R China
14.Zhejiang Univ, Collaborat Innovat Ctr Diag & Treatment Infect Di, Hangzhou 310003, Zhejiang, Peoples R China
推荐引用方式
GB/T 7714
Zhou, Bin,Dong, Hui,He, Yungang,et al. Composition and Interactions of Hepatitis B Virus Quasispecies Defined the Virological Response During Telbivudine Therapy[J]. SCIENTIFIC REPORTS,2015,5.
APA Zhou, Bin.,Dong, Hui.,He, Yungang.,Sun, Jian.,Jin, Weirong.,...&Hou, Jinlin.(2015).Composition and Interactions of Hepatitis B Virus Quasispecies Defined the Virological Response During Telbivudine Therapy.SCIENTIFIC REPORTS,5.
MLA Zhou, Bin,et al."Composition and Interactions of Hepatitis B Virus Quasispecies Defined the Virological Response During Telbivudine Therapy".SCIENTIFIC REPORTS 5(2015).
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