Specific expression of human interferon-gamma controls hepatitis B virus replica

StephenW

J Virol Methods. 2012 Mar;180(1-2):84-90. Epub  2012 Jan 5.
Specific expression of human interferon-gamma controls hepatitis B virus replication in vitro in secreting hepatitis B surface antigen hepatocytes.Kan Q, Li D, Yu Z.
SourceThe First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450052, China. [email protected]

AbstractInterferon-gamma (IFN-γ) has been reported to have antiviral activity against Hepatitis B virus (HBV) and to suppress HBV replication noncytolytically in vivo. Since systemic administration of IFN-γ may cause severe adverse effects, studies of the effects of liver-specific IFN-γ expression from adenoviral vectors in vivo have been investigated. In this study, a novel strategy has been described that drives specific expression of human IFN-γ in HBsAg-secreting hepatocytes. A bicistronic expression vector has been developed, pcDNA3.1-HBV antisense S gene-HCV core protein gene-HCV internal ribosome entry sites (IRES)-IFN-γ (pcDNA-SCIγ), by inserting four DNA fragments into pcDNA3.1. Tight modulation of HCV IRES-dependent translation by the HCV core protein was achieved using an antisense RNA technique with a bicistronic expression vector. HepG2 cells and HepG2.2.15 cells stably expressing HBV were transduced with pcDNA-SCIγ to test the responsiveness of IFN-γ to HBsAg expression. Gene transfer resulted in a low background and a 30-fold induction of IFN-γ expression from pcDNA-SCIγ in a cell-specific fashion. Hepatocyte-specific IFN-γ expression controlled effectively HBV replication in HBsAg-secreting HepG2.2.15 cells without cell toxicity.
Copyright © 2012 Elsevier B.V. All rights reserved.

StephenW

J病毒学方法。 201203180（1-2）:84-90。 1月5 EPUB2012。
特异性表达人干扰素-γ分泌乙肝表面抗原肝细胞的体外控制乙肝病毒复制。
阚强，李德生，余Z.
源

第一附属医院，郑州大学，河南郑州450052，中国。 [email protected]
抽象

γ-干扰素（γ-干扰素）已报告有对乙肝病毒（HBV）的抗病毒活性和抑制体内HBV复制noncytolytically。由于γ-干扰素全身用药可能会导致严重的副作用，对肝脏特异性γ-干扰素在体内的腺病毒载体表达的影响的研究已经展开调查。在这项研究中，一种新的战略已被描述，驱动器的人乙肝表面抗原，肝细胞分泌γ-干扰素的具体体现。已经制定一个双顺反子表达载体，反义质粒pcDNA3.1-HBV的S基因的丙型肝炎病毒核心蛋白基因丙型肝炎病毒内部核糖体进入位点（IRES的），干扰素-γ（载体pcDNA-SCIγ），由4个DNA片段插入到pcDNA3.1。由丙型肝炎病毒核心蛋白的丙型肝炎病毒IRES的依赖翻译的紧张调制使用了双顺反子表达载体的反义RNA技术实现。 HepG2细胞和HepG2.2.15细胞稳定表达乙型肝炎病毒转染载体pcDNA-SCIγ测试的反应干扰素γ-HBsAg的表达。基因转移，导致在一个较低的背景和在细胞特异性的方式为pcDNA-SCIγ的γ-干扰素表达的30倍，从感应。肝细胞特异性IFN-γ的表达有效控制乙型肝炎病毒复制的乙肝表面抗原分泌HepG2.2.15细胞无细胞毒性。

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