Min Saehong, Lim Yun-Sook, Shin Dongjo, Park Chorong, Park Jae-Bong, Kim Seungtaek, Windisch Marc P, Hwang Soon B
Department of Biomedical Gerontology, Graduate School of Hallym UniversityChuncheon, South Korea.
National Research Laboratory of Hepatitis C Virus and Ilsong Institute of Life Science, Hallym UniversityAnyang, South Korea.
Front Microbiol. 2017 Jun 19;8:1129. doi: 10.3389/fmicb.2017.01129. eCollection 2017.
Abl is a central regulator of multiple cellular processes controlling actin dynamics, proliferation, and differentiation. Here, we showed that knockdown of Abl impaired hepatitis C virus (HCV) propagation. Treatment of Abl tyrosine kinase-specific inhibitor, imatinib and dasatinib, also significantly decreased HCV RNA and protein levels in HCV-infected cells. We showed that both imatinib and dasatinib selectively inhibited HCV infection at the entry step of HCV life cycle, suggesting that Abl kinase activity may be necessary for HCV entry. Using HCV pseudoparticle infection assays, we verified that Abl is required for viral entry. By employing transferrin uptake and immunofluorescence assays, we further demonstrated that Abl was involved in HCV entry at a clathrin-mediated endocytosis step. These data suggest that Abl may represent a novel host factor for HCV entry.
Abl是控制肌动蛋白动力学、增殖和分化的多个细胞过程的核心调节因子。在此，我们表明敲低Abl会损害丙型肝炎病毒（HCV）的传播。用Abl酪氨酸激酶特异性抑制剂伊马替尼和达沙替尼处理，也显著降低了HCV感染细胞中的HCV RNA和蛋白质水平。我们表明伊马替尼和达沙替尼在HCV生命周期的进入步骤选择性抑制HCV感染，提示Abl激酶活性可能是HCV进入所必需的。使用HCV假病毒颗粒感染试验，我们证实病毒进入需要Abl。通过采用转铁蛋白摄取和免疫荧光试验，我们进一步证明Abl在网格蛋白介导的内吞作用步骤参与HCV进入。这些数据表明Abl可能是HCV进入的一个新的宿主因子。
