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学科主题: 基础医学
题名:
A laboratory-adapted HCV JFH-1 strain is sensitive to neutralization and can gradually escape under the selection pressure of neutralizing human plasma
作者: Song, Hongshuo1,2; Ren, Furong3; Li, Jin1,2; Shi, Shuang1,2; Yan, Ling1,2; Gao, Feng4; Li, Kui5; Zhuang, Hui1,2
关键词: HCV ; Cell culture adaptation ; Neutralization ; Escape mutation
刊名: VIRUS RESEARCH
发表日期: 2012-10-01
DOI: 10.1016/j.virusres.2012.07.022
卷: 169, 期:1, 页:154-161
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Virology
研究领域[WOS]: Virology
关键词[WOS]: HEPATITIS-C-VIRUS ; E2 ENVELOPE GLYCOPROTEIN ; SCAVENGER RECEPTOR-BI ; IMMUNODEFICIENCY-VIRUS ; MONOCLONAL-ANTIBODIES ; IN-VITRO ; INFECTION ; CELL ; TYPE-1 ; CD81
英文摘要:

Viral replication and neutralization of hepatitis C viruses (HCV) have been studied using the infectious molecular clone JFH-1. By passaging JFH-1 in hepatoma cells in the absence or presence of HCV neutralizing antibodies (nAbs), we investigated the molecular mechanisms of cell-culture adaptation and sensitivity to nAbs. The cell culture-adapted JFH-1 virus (JFH-1-CA) became more sensitive to nAbs than its parental virus. Sequence analysis revealed that the predominant viruses in the JFH-1-CA population carried two mutations in their envelopes (1414T and V293A). Plasma that could neutralize JFH-1-CA was found in 2 of 7 HCV-infected individuals who have cleared the virus in blood. Plasma 226233 with a higher 50% neutralization titer was used for in vitro selection of neutralization resistant viruses. Under the increasing selection pressure of plasma 226233, the neutralizing sensitivity of JFH-1-CA decreased gradually. Two mutations (T414I and P500S) in envelope were found in all but one sequenced clones in the viral population after eight rounds of selection. Interestingly, the cell-culture adapted mutation I414T reverted back to the wild-type residue (1414) under the selection pressure. By introducing mutations at positions 414 and 500 into the JFH-1 clone, we confirmed that the T414I mutation alone can confer neutralization resistance. The results of this current study suggest that nAbs are present in a subset of HCV-infected individuals who have cleared the virus in blood. Our data also provide the first evidence that, the E2 residue P500, located within a previously identified highly conserved polyclonal epitope, may be a target for neutralizing antibodies present in individual who have spontaneously resolved the HCV infection. Published by Elsevier B.V.

语种: 英语
所属项目编号: 2008ZX10002-013 ; AI069285
项目资助者: Major Science and Technology Special Project of China Eleventh Five-year Plan ; US National Institutes of Health
WOS记录号: WOS:000311133800019
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/56973
Appears in Collections:基础医学院_病原生物学系_期刊论文

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作者单位: 1.Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Dept Microbiol, Beijing 100191, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Ctr Infect Dis, Beijing 100191, Peoples R China
3.Beijing Red Cross Blood Ctr, Beijing 100088, Peoples R China
4.Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC 27710 USA
5.Univ Tennessee, Ctr Hlth Sci, Dept Microbiol Immunol & Biochem, Memphis, TN 38163 USA

Recommended Citation:
Song, Hongshuo,Ren, Furong,Li, Jin,et al. A laboratory-adapted HCV JFH-1 strain is sensitive to neutralization and can gradually escape under the selection pressure of neutralizing human plasma[J]. VIRUS RESEARCH,2012,169(1):154-161.
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