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学科主题: 临床医学
题名:
In vitro resistance to interferon of hepatitis B virus with precore mutation
作者: Wang, Yan; Wei, Lai; Jiang, Dong; Cong, Xu; Fei, Ran; Xiao, Jiang; Wang, Yu
关键词: Hepatitis B virus ; Mutation ; Interferon ; Viral resistance
刊名: WORLD JOURNAL OF GASTROENTEROLOGY
发表日期: 2005-02-07
卷: 11, 期:5, 页:649-655
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Gastroenterology & Hepatology
研究领域[WOS]: Gastroenterology & Hepatology
英文摘要:

AIM: Chronic hepatitis B virus (HBV) infection is predominantly treated with interferon alpha (IFN-alpha), which results in an efficient reduction of the viral load only in 20-40% of treated patients. Mutations at HBV precore prevail in different clinical status of HBV infection. The roles of precore mutation in the progression of chronic hepatitis and interferon sensitivity are still unknown. The aim of this study was to explore if there was any relationship between HBV precore mutation and sensitivity to interferon in vitro.

METHODS: HBV replication-competent recombinant constructs with different patterns of precore mutations were developed. Then the recombinants were transiently transfected into hepatoma cell line (Huh7) by calcium phosphate transfection method. With or without IFN, viral products in culture medium were collected and quantified 3 d after transfection.

RESULTS: We obtained 4 recombinant constructs by orientation-cloning 1.2-fold-overlength HBV genome into pUC18 vector via the EcoRI and Hind III and PCR mediated site-directed mutagenesis method. All the recombinants contained mutations within precore region. Huh7 cells transfected with recombinants secreted HBsAg and HBV particles into the cell culture medium, indicating that all the recombinants were replication-competent. By comparing the amount of HBV DNA in the medium, we found that HBV DNA in medium reflecting HBV replication efficiency was different in different recombinants. Recombinants containing precore mutation had fewer HBV DNAs in culture medium than wild type. This result showed that recombinants containing precore mutation had lower replication efficiency than wild type. HBV DNA was decreased in pUC18-HBV1.2-WT recombinants after IFN was added while others with precore mutations were not, indicating that HBV harboring precore mutation was less sensitive to IFN in cell culture system.

CONCLUSION: These data indicate that HBV harboring precore mutation may be resistant to IFN in vitro. (C) 2005 The WJG Press and Elsevier Inc. All rights reserved.

语种: 英语
所属项目编号: G1999054106
项目资助者: Major State Basic Research Development Program of China (973 Program)
WOS记录号: WOS:000208100100007
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/52072
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: Peking Univ, Peoples Hosp, Inst Hepatol, Beijing 100044, Peoples R China

Recommended Citation:
Wang, Yan,Wei, Lai,Jiang, Dong,et al. In vitro resistance to interferon of hepatitis B virus with precore mutation[J]. WORLD JOURNAL OF GASTROENTEROLOGY,2005,11(5):649-655.
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