TY - JOUR
T1 - The RNA Sensor RIG-I Dually Functions as an Innate Sensor and Direct Antiviral Factor for Hepatitis B Virus
AU - Sato, Seiichi
AU - Li, Kai
AU - Kameyama, Takeshi
AU - Hayashi, Takaya
AU - Ishida, Yuji
AU - Murakami, Shuko
AU - Watanabe, Tsunamasa
AU - Iijima, Sayuki
AU - Sakurai, Yu
AU - Watashi, Koichi
AU - Tsutsumi, Susumu
AU - Sato, Yusuke
AU - Akita, Hidetaka
AU - Wakita, Takaji
AU - Rice, Charles M.
AU - Harashima, Hideyoshi
AU - Kohara, Michinori
AU - Tanaka, Yasuhito
AU - Takaoka, Akinori
N1 - Funding Information:
We thank M. Hijikata and K. Shimotohno for HuS-E/2 cell line, N. Sakamoto for Huh-7.5.1/Rep-Feo-1b cells, J. Miyazaki for pCAGGS vector, A. Miyawaki for pCAGGS-YFP vector, T. Fujita for the luciferase reporter plasmid p-55C1BLuc, A. Takada for VSV, H. Kida for NDV, H. Ishizu and T. Hirose for technical advice on RIP assay, and A. Bergthaler, A. Shlomai, T. Saito, and M. Yasuda for critical reading of the manuscript and helpful advice. The authors are grateful for financial supports from the Ministry of Health, Labour and Welfare of Japan (Grant-in-Aid to A.T. and Y.T.), the Ministry of Education, Culture, Sports, Science and Technology of Japan (Grant-in-Aid for Scientific Research [A] [25253030] to A.T., Grant-in-Aid for Scientific Research on Innovative Areas [25115502, 23112701] to A.T., Grant-in-Aid for Young Scientists [B] [25870015] to S.S.), IRYO HOJIN SHADAN JIKOKAI (H. Tanaka and N. Takayanagi) to A.T., the Kato Memorial Bioscience Foundation to A.T., the Yasuda Medical Foundation to A.T., the Takeda Science Foundation to A.T., and The Waksman Foundation of Japan to A.T. Y.I. is an employee of PhoenixBio.
Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/1/20
Y1 - 2015/1/20
N2 - Host 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 nottype 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.
AB - Host 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 nottype 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.
UR - http://www.scopus.com/inward/record.url?scp=84921280194&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84921280194&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2014.12.016
DO - 10.1016/j.immuni.2014.12.016
M3 - Article
C2 - 25557055
AN - SCOPUS:84921280194
SN - 1074-7613
VL - 42
SP - 123
EP - 132
JO - Immunity
JF - Immunity
IS - 1
ER -
