Sakamoto Naoya, Yoshimura Mika, Kimura Tomomi, Toyama Keisuke, Sekine-Osajima Yuko, Watanabe Mamoru, Muramatsu Masaaki
Department for Hepatitis Control, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Biochem Biophys Res Commun. 2007 Jun 1;357(2):467-73. doi: 10.1016/j.bbrc.2007.03.167. Epub 2007 Apr 5.
Various cytokines contribute to control hepatitis C virus (HCV) viral replication. HCV subgenomic replicon systems have been developed, and cell-cycle-dependent replication has been reported. But the molecules involved in this processes is not totally elucidated. The aim of this study is to investigate the involvement of the bone morphogenetic protein (BMP)-7, a member of TGF-beta superfamily, to the in vitro HCV replication. BMP-7 dose-dependently suppressed the replication and protein expression from the HCV replicon in Huh7/Rep-Feo cells and was associated with cell-cycle arrest at the G1 phase. These results were consistent with the effect of TGF-beta in a previous study. Combination of BMP-7 and interferon-alpha showed a synergic decrease of HCV replication, and was more effective compared to the treatment with interferon-alpha alone. This synergistic effect was also present in HCV-JFH1 virus cell culture. While BMP-7 alone did not stimulate expression of the interferon-stimulated genes (ISGs), it augmented interferon-induced expression of the ISGs independently of the interferon-induced Jak/STAT pathway. Taken together, BMP-7 may constitute a novel molecule to suppress HCV replication.
多种细胞因子有助于控制丙型肝炎病毒（HCV）的病毒复制。HCV亚基因组复制子系统已被开发出来，并且有报道称存在细胞周期依赖性复制。但参与这一过程的分子尚未完全阐明。本研究的目的是探讨转化生长因子-β超家族成员骨形态发生蛋白（BMP）-7对体外HCV复制的影响。BMP-7以剂量依赖的方式抑制Huh7/Rep-Feo细胞中HCV复制子的复制和蛋白表达，并与细胞周期停滞在G1期有关。这些结果与先前研究中转化生长因子-β的作用一致。BMP-7与α干扰素联合使用可协同降低HCV复制，且比单独使用α干扰素治疗更有效。这种协同作用在HCV-JFH1病毒细胞培养中也存在。虽然单独的BMP-7不会刺激干扰素刺激基因（ISG）的表达，但它可独立于干扰素诱导的Jak/STAT途径增强干扰素诱导的ISG表达。综上所述，BMP-7可能是一种抑制HCV复制的新分子。
