Regulation of hepatitis C virus replication by the core protein through its interaction with viral RNA polymerase.
The hepatitis C virus (HCV) core protein is a structural component of the nucleocapsid and has been shown to modulate cellular signaling pathways by interaction with various cellular proteins. In the present study, we investigated the role of HCV core protein in viral RNA replication. Immunoprecipitation experiments demonstrated that the core protein binds to the amino-terminal region of RNA-dependent RNA polymerase (RdRp), which encompasses the finger and palm domains. Direct interaction between HCV RdRp and core protein led to inhibition of RdRp RNA synthesis activity of in vitro. Furthermore, over-expression of core protein, but not its derivatives lacking the RdRp-interacting domain, suppressed HCV replication in a hepatoma cell line harboring an HCV subgenomic replicon RNA. Collectively, our results suggest that the core protein, through binding to RdRp and inhibiting its RNA synthesis activity, is a viral regulator of HCV RNA replication.
Kang
Su-Min
SM
Department of Biotechnology, Yonsei University, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-749, Republic of Korea.
Choi
Jin-Kyu
JK
Kim
Seong-Jun
SJ
Kim
Jung-Hee
JH
Ahn
Dae-Gyun
DG
Oh
Jong-Won
JW
D045744:Cell Line, Tumor; D016174:Hepacivirus / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D047468:Immunoprecipitation; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D012367:RNA, Viral / Q000378:metabolism*; D012324:RNA-Dependent RNA Polymerase / Q000378:metabolism*; D014758:Viral Core Proteins / Q000235:genetics / Q000378:metabolism*; D017361:Viral Nonstructural Proteins / Q000378:metabolism*; D014779:Virus Replication
D012367:RNA, Viral; D014758:Viral Core Proteins; D017361:Viral Nonstructural Proteins; C069130:nucleocapsid protein, Hepatitis C virus; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase