Hepatitis C virus core protein is a potent inhibitor of RNA silencing-based antiviral response.
OBJECTIVE
Persistent infection with hepatitis C virus (HCV) leads to chronic hepatitis and hepatocellular carcinoma (HCC). RNA interference (RNAi) may act as a host antiviral response against viral RNA.


METHODS
The effects of RNAi on both the replicative intermediates and the internal ribosome entry site (IRES) of HCV were studied by using HCV-related short interfering RNA (siRNA) detection assay. The mechanism that permits HCV to escape RNAi was studied by using RNAi assay materials.


RESULTS
These studies demonstrate that the Dicer, an RNase enzyme that generates short siRNA, can target and digest both the IRES and the replicative intermediate of HCV into siRNA of approximately 22 nucleotides. Further studies also show that Dicer can inhibit the replication of the HCV subgenomic replicon. However, the HCV core protein inhibits this RNAi and rescues the replication of the HCV subgenomic replicon through a direct interaction with Dicer.


CONCLUSIONS
RNAi is a limiting factor for HCV infection, and the core protein suppresses the RNA silencing-based antiviral response. This ability of the core protein to counteract the host defense may lead to a persistent viral infection and may contribute to the pathogenesis of HCV.
Wang
Yue
Y
Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan. euy-tokyo@umin.ac.jp
Kato
Naoya
N
Jazag
Amarsanaa
A
Dharel
Narayan
N
Otsuka
Motoyuki
M
Taniguchi
Hiroyoshi
H
Kawabe
Takao
T
Omata
Masao
M
D002460:Cell Line; D006526:Hepatitis C / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D034622:RNA Interference; D012093:Replicon; D043244:Ribonuclease III / Q000502:physiology; D014758:Viral Core Proteins / Q000737:chemistry / Q000502:physiology*; D014779:Virus Replication
D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D043244:Ribonuclease III