Bone morphogenetic protein-7 and interferon-alpha synergistically suppress hepatitis C virus replicon.
Bone morphogenetic protein-7 and interferon-alpha synergistically suppress hepatitis C virus replicon.
复制标题
DOI：
10.1016/j.bbrc.2007.03.167
复制
发表时间：
2007-06
影响因子：
3.1
通讯作者：
N. Sakamoto;M. Yoshimura;Tomomi Kimura;K. Toyama;Yuko Sekine‐Osajima;Mamoru Watanabe;M. Muramatsu
中科院分区：
文献类型：
--
作者：
N. Sakamoto;M. Yoshimura;Tomomi Kimura;K. Toyama;Yuko Sekine‐Osajima;Mamoru Watanabe;M. Muramatsu
各种细胞因子有助于控制丙型肝炎病毒（HCV）的病毒复制。已经开发了HCV亚基因组复制子系统，并且已经报道了细胞周期依赖性复制。但参与这一过程的分子并没有完全阐明。本研究旨在探讨TGF-β超家族成员骨形态发生蛋白（BMP）-7对HCV体外复制的影响。BMP-7剂量依赖性地抑制Huh 7/Rep-Feo细胞中HCV复制子的复制和蛋白表达，并与G1期的细胞周期停滞相关。这些结果与先前研究中TGF-β的作用一致。BMP-7和干扰素-α的组合显示出协同降低HCV复制，并且与单独使用干扰素-α的治疗相比更有效。这种协同作用也存在于HCV-JFH 1病毒细胞培养物中。虽然单独的BMP-7不刺激干扰素刺激基因（ISGs）的表达，但它增强了干扰素诱导的ISGs的表达，而不依赖于干扰素诱导的Jak/STAT途径。总之，BMP-7可能构成抑制HCV复制的新分子。
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-β 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-β 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.