@article{mbs:/content/journal/jgv/10.1099/vir.0.83056-0, author = "Tasaka, Megumi and Sakamoto, Naoya and Itakura, Yoshie and Nakagawa, Mina and Itsui, Yasuhiro and Sekine-Osajima, Yuko and Nishimura-Sakurai, Yuki and Chen, Cheng-Hsin and Yoneyama, Mitsutoshi and Fujita, Takashi and Wakita, Takaji and Maekawa, Shinya and Enomoto, Nobuyuki and Watanabe, Mamoru", title = "Hepatitis C virus non-structural proteins responsible for suppression of the RIG-I/Cardif-induced interferon response", journal= "Journal of General Virology", year = "2007", volume = "88", number = "12", pages = "3323-3333", doi = "https://doi.org/10.1099/vir.0.83056-0", url = "https://www.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.83056-0", publisher = "Microbiology Society", issn = "1465-2099", type = "Journal Article", abstract = "Viral infections activate cellular expression of type I interferons (IFNs). These responses are partly triggered by RIG-I and mediated by Cardif, TBK1, IKKϵ and IRF-3. This study analysed the mechanisms of dsRNA-induced IFN responses in various cell lines that supported subgenomic hepatitis C virus (HCV) replication. Transfection of dsRNA into Huh7, HeLa and HEK293 cells induced an IFN expression response as shown by IRF-3 dimerization, whilst these responses were abolished in corresponding cell lines that expressed HCV replicons. Similarly, RIG-I-dependent activation of the IFN-stimulated response element (ISRE) was significantly suppressed by cells expressing the HCV replicon and restored in replicon-eliminated cells. Overexpression analyses of individual HCV non-structural proteins revealed that NS4B, as well as NS34A, significantly inhibited RIG-I-triggered ISRE activation. Taken together, HCV replication and protein expression substantially blocked the dsRNA-triggered, RIG-I-mediated IFN expression response and this blockade was partly mediated by HCV NS4B, as well as NS34A. These mechanisms may contribute to the clinical persistence of HCV infection and could constitute a novel antiviral therapeutic target.", }