The RNA Sensor RIG-I Dually Functions as an Innate Sensor and Direct Antiviral Factor for Hepatitis B Virus
The RNA Sensor RIG-I Dually Functions as an Innate Sensor and Direct Antiviral Factor for Hepatitis B Virus
Sato S, Li K, Kameyama T, Hayashi T, Ishida Y, Murakami S, Watanabe T, Iijima S, Sakurai Y, Watashi K, Tsutsumi S, Sato Y, Akita H, Wakita T, Rice CM, Harashima H, Kohara M, Tanaka Y, Takaoka A.
Immunity 2015, 42(1): 123-132.
Speaker: Li-Chun Wang (王立君) Time: 13:00~14:00, Jun 03, 2015
Commentator: Dr. Cheng-Chan Lu (呂政展 老師) Place: Room 601
Abstract:
Approximately four hundred million people worldwide are persistently infected with Hepatitis B virus (HBV) and the infection is a major cause of inflammation, cirrhosis and cancer of the liver.1 Currently, the therapies have limited efficacy by interferon (IFN) and nucleoside/nucleotide analogs.2 However, it is still not fully clarified how HBV is recognized by human hepatocytes and the role of type III IFNs in HBV infection as well. This study found that HBV infection induced type III IFNs instead of type I IFNs. Knockdown experiments demonstrated that HBV infection was dependent on RIG-I and its downstream signaling components to induce type III IFNs activation. HBV has a circular, partially double-stranded DNA genome that is replicated by reverse transcription of a pregenomic RNA (pgRNA). The author found that the pgRNA of HBV was a major component to induce type III IFNs expression. In addition, the 5’ ε region of thepgRNA, which forms stem-loop structure, was required for RIG-I-mediated type III IFNs production. They further demonstrated that ε RNA directly bound the C-terminal repressor domain (RD) of RIG-I. In addition to acting as a sensor, RIG-I was also shown to function as an effector to interfere with viral replication by competing with the HBV P protein binding to the pgRNA. Finally, the author designed a vector encoding ε RNA to test its therapeutic potential to inhibit HBV replication in the humanized mouse liver. Taken together, the author revealed the dual function of RIG-I as an HBV sensor activating innate signaling to produce type III IFNs and as a direct antiviral factor counteracting viral P protein binding to pgRNA.
References：
1. Halegoua-De Marzio D, Hann HW. Then and now: the progress in hepatitis B treatment over the past 20 years. World journal of gastroenterology : WJG 2014, 20(2): 401-413.
2. Rehermann B, Nascimbeni M. Immunology of hepatitis B virus and hepatitis C virus infection. Nature reviews Immunology 2005, 5(3): 215-229.