2024-03-29T09:52:08Zhttps://eprints.lib.hokudai.ac.jp/dspace-oai/requestoai:eprints.lib.hokudai.ac.jp:2115/626202022-11-17T02:08:08Zhdl_2115_20058hdl_2115_149The RNA Sensor RIG-I Dually Functions as an Innate Sensor and Direct Antiviral Factor for Hepatitis B VirusRIG-I functions as a dual effector against HBVSato, SeiichiLi, KaiKameyama, TakeshiHayashi, TakayaIshida, YujiMurakami, ShukoWatanabe, TsunamasaIijima, SayukiSakurai, YuWatashi, KoichiTsutsumi, SusumuSato, YusukeAkita, HidetakaWakita, TakajiRice, Charles M.Harashima, HideyoshiKohara, MichinoriTanaka, YasuhitoTakaoka, Akinori490Host innate recognition triggers key immune responses for viral elimination. The sensing mechanism of hepatitis B virus (HBV), a DNA virus, and the subsequent downstream signaling events remain to be fully clarified. Here we found that type III but not type I interferons are predominantly induced in human primary hepatocytes in response to HBV infection, through retinoic acid-inducible gene-I (RIG-I)-mediated sensing of the 5'-ε region of HBV pregenomic RNA. In addition, RIG-I could also counteract the interaction of HBV polymerase (P protein) with the 5'-ε region in an RNA-binding dependent manner, which consistently suppressed viral replication. Liposome-mediated delivery and vector-based expression of this ε region-derived RNA in liver abolished the HBV replication in human hepatocyte-chimeric mice. These findings identify an innate recognition mechanism by which RIG-I dually functions as an HBV sensor activating innate signaling and to counteract viral polymerase in human hepatocytes.Cell PressJournal Articleapplication/pdfhttp://hdl.handle.net/2115/62620https://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/62620/3/Immunity42_123.pdf1074-7613Immunity4211231322015-01-20enginfo:pmid/25557055info:doi/10.1016/j.immuni.2014.12.016© 2015. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/author