Interferon-gamma controls HBV replication

StephenW

http://www.ncbi.nlm.nih.gov/pubmed/22240074
J Virol Methods. 2012 Jan 5. [Epub ahead of print]
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, No. 1 Jianshe Road, Zhengzhou, Henan 450052, China.

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.

StephenW

J Virol方法。 2012年1月5。 [检索提前打印]
人干扰素-γ的特异性表达控制在体外分泌乙肝表面抗原肝细胞乙型肝炎病毒复制。
阚强，李达，于Z。
来源

第一附属医院，郑州市建设路1号，郑州大学，河南450052，中国。
摘要

γ-干扰素（IFN -γ）据报道，对B型肝炎病毒（HBV）的抗病毒活性，抑制体内HBV复制noncytolytically。由于全身给药的IFN -γ可能会造成严重的不利影响，研究肝脏特异性IFN -γ在体内的腺病毒载体表达的影响进行了研究。在这项研究中，一种新的战略已被描述的驱动器人的HBsAg分泌肝细胞中IFN -γ的具体体现。已开发一个双顺反子表达载体，质粒pcDNA3.1 - HBV的反义小号基因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），干扰素-γ（pcDNA -SCIγ），由四个DNA片段插入质粒pcDNA3.1。丙型肝炎病毒的IRES依赖由丙型肝炎病毒核心蛋白翻译的紧密调制是利用反义RNA技术与双顺反子表达载体来实现。稳定表达HBV的HepG2细胞和HepG2.2.15细胞转导pcDNA -SCIγ测试的响应干扰素γHBsAg的表达。基因转移，导致在低背景和30倍的IFN -γ表达诱导pcDNASCIγ在一个特定的细胞的方式。肝细胞特异性IFN -γ表达的有效控制乙肝病毒复制的乙肝表面抗原分泌HepG2.2.15细胞无细胞毒性。

乙肝病毒滴度增加雌性小鼠卵巢切除后，在与雌激素补充雄性小鼠减少。肝“雌激素受体（ER）α的表达增加雌激素暴露。在HepG2细胞中，ERα的上调减少乙肝病毒的转录，这需要一个特定区域内增强剂一直接的DNA结合ERα和组蛋白去乙酰化酶活性并不需要ERA -介导的HBV基因的镇压。过表达肝细胞核因子（HNF）4α，结合本地区，克服了ERα的镇压效果。并没有抑制ERα的乙型肝炎病毒复制子的转录增强剂一突变HNF4ą结合现场免疫共沉淀分析表明ERA和HNF4α之间的相互作用，这种相互作用阻止HNF4ą约束力增强剂我和乙肝病毒转录激活。
结论：

通过上调ERα的，交互和改变HNF4α约束力HBV的增强一，这些研究结果可能会考虑降低病毒载量和降低肝癌的发病率在乙肝病毒感染的妇女比男性雌激素可以抑制乙肝病毒基因的转录。

MP4

http://newpaper.dahe.cn/hnrb/html/2011-01/05/content_447051.htm