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学科主题: 临床医学
题名:
rtE218G, a novel hepatitis B virus mutation with resistance to adefovir dipivoxil in patients with chronic hepatitis B
作者: Liu, L. J.1; Wang, J. H.1; Du, S. C.1; Tian, J. H.1,2; Yang, R. F.1; Wei, L.1
关键词: adefovir ; hepatitis B virus ; mutation ; resistance
刊名: JOURNAL OF VIRAL HEPATITIS
发表日期: 2010-03-01
DOI: 10.1111/j.1365-2893.2010.01273.x
卷: suppl.1, 页:66-72
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Gastroenterology & Hepatology ; Infectious Diseases ; Virology
研究领域[WOS]: Gastroenterology & Hepatology ; Infectious Diseases ; Virology
关键词[WOS]: LONG-TERM THERAPY ; LIVER-TRANSPLANTATION ; DRUG-RESISTANCE ; POLYMERASE ; MECHANISMS ; REPLICATION ; SELECTION ; VARIANT ; ADV
英文摘要:

Antiviral therapy is a potentially successful approach for the treatment of patients with Hepatitis B virus (HBV) infection. One antiviral agent is the nucleoside analogue adefovir dipivoxil (ADV). Its efficiency is compromised by the emergence of drug-resistant HBV mutants. Although three major ADV-resistant mutations of HBV are known, rtA181T/V and rtN236T, HBV mutations associated with ADV resistance have not been fully identified. We analyzed DNA sequences that covered a 244 base pair region of the HBV polymerase gene from patients with clinical manifestations of ADV resistance. A novel pattern of amino acid substitutions in HBV polymerase was detected in 26 out of 86 patients. This mutant exhibited a substitution of glycine for glutamic acid at residue 218 (rtE218G). Transient transfection of the HBV replication-competent construct including the rtE218G mutation was performed in HepG2 cells in order to determine the relevance of this mutation to ADV resistance. Phenotypic analyses demonstrated that the rtE218G mutation could independently confer resistance to ADV in vitro, with a 50% inhibitory concentration (IC(50)) 5.5-fold higher than wild-type HBV. RtE218G-mutated HBV also showed a decreased replication capacity in vitro, equal to 87% of wild-type HBV. The present study showed that the rtE218G mutation may be a novel ADV-resistant mutation. Further work will focus on resistance surveillance and cross-resistance analyses, and the molecular mechanisms involved.

语种: 英语
所属项目编号: 2005CB522902 ; 2007CB512900 ; 2006AA02A410 ; 30571639 ; 30901256 ; 2008ZX10002-012 ; 2008ZX10002-013 ; 7102153
项目资助者: Chinese Basic Research Foundation 973 program ; 863 program ; National Natural Science Foundation of China ; National Science and Technology Key Major Project for Infectious Diseases Control during the Eleventh Five-Year Plan Period ; Beijing Municipal Natural Science Foundation ; Key Clinical Research Program of the Ministry of Health
WOS记录号: WOS:000275184400011
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/51972
Appears in Collections:北京大学第二临床医学院_北京大学肝病研究所_期刊论文

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作者单位: 1.Beijing Ditan Hosp, Dept Lab Med, Beijing, Peoples R China
2.Peking Univ, Inst Hepatol, Peoples Hosp, Beijing 100044, Peoples R China

Recommended Citation:
Liu, L. J.,Wang, J. H.,Du, S. C.,et al. rtE218G, a novel hepatitis B virus mutation with resistance to adefovir dipivoxil in patients with chronic hepatitis B[J]. JOURNAL OF VIRAL HEPATITIS,2010,suppl.1:66-72.
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