Liu Feng-Jun, Chen En-Qiang, Zhou Qiao-Ling, Zhou Tao-You, Liu Cong, Liu Li, Cheng Xing, Tang Hong
Center of Infectious Diseases, West China Hospital of Sichuan University, No.37 Guo Xue Xiang, Chengdu, 610041 People's Republic of China ; Division of Infectious Diseases, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, 610041 People's Republic of China ; Department of Infectious Diseases, North Sichuan Medical College, Nanchong, 637000 People's Republic of China.
Indian J Virol. 2012 Dec;23(3):278-85. doi: 10.1007/s13337-012-0091-2. Epub 2012 Sep 6.
The roles of interferon regulatory element (IRE) in Hepatitis B virus (HBV) genome on inhibitory effect of interferon against HBV are controversial in vitro. This study aimed to determine the functional characterization of HBV-IRE sequence in vivo. Wild-type or IRE-mutant HBV replication-competent mice were firstly established, and mice were subquently treated with polyinosinic-polytidylin acid (polyI.C) or phosphate-buffered saline via intraperitoneal. Results showed that PolyI.C inhibited viral replication, and increased the level of 2',5'-oligoadenylate synthase mRNA transcripts, a marker of INF-α/β induction. Between wild-type and IRE-mutant HBV replication-competent mice, the levels of HBV-RNA and HBV-DNA replication intermediates were similar. After PolyI.C treatment, the decreasing of HBV-RNA was similar between two groups, but HBV-DNA replication intermediates decreased significantly less in IRE-mutant than wild-type HBV replication-competent mice. These findings suggested that IRE mutant reduced the inhibitory effect of interferon on HBV replication, which played a role in antiviral effect of interferon against HBV.
在体外,干扰素调节元件(IRE)在乙型肝炎病毒(HBV)基因组中对干扰素抑制HBV的作用存在争议。本研究旨在确定HBV-IRE序列在体内的功能特性。首先建立野生型或IRE突变型具有HBV复制能力的小鼠,随后通过腹腔注射用聚肌苷酸-聚胞苷酸(polyI.C)或磷酸盐缓冲盐水处理小鼠。结果显示,polyI.C抑制病毒复制,并增加2',5'-寡腺苷酸合成酶mRNA转录物水平,这是INF-α/β诱导的标志物。在野生型和IRE突变型具有HBV复制能力的小鼠之间,HBV-RNA和HBV-DNA复制中间体的水平相似。PolyI.C处理后,两组之间HBV-RNA的降低相似,但IRE突变型小鼠中HBV-DNA复制中间体的降低明显少于野生型具有HBV复制能力的小鼠。这些发现表明,IRE突变降低了干扰素对HBV复制的抑制作用,其在干扰素抗HBV的抗病毒作用中发挥作用。