Hepatitis C virus NS2 protein activates cellular cyclic AMP-dependent pathways.
Chronic infection of the hepatitis C virus (HCV) leads to liver cirrhosis and cancer. The mechanism leading to viral persistence and hepatocellular carcinoma, however, has not been fully understood. In this study, we show that the HCV infection activates cellular cAMP-dependent pathways. Expression of a luciferase reporter gene controlled by a basic promoter with the cAMP response element (CRE) was significantly elevated in human hepatoma Huh-7 cells infected with the HCV JFH1. Analysis with viral subgenomic replicons indicated that the HCV NS2 protein is responsible for the effect. Furthermore, the level of cellular transcripts whose stability is known to be regulated by cAMP was specifically reduced in cells harboring NS2-expressing replicons. These results allude to the HCV NS2 protein having a novel function of regulating cellular gene expression and proliferation through the cAMP-dependent pathway.
Kim
Kyoung Mi
KM
School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
Kwon
Shi-Nae
SN
Kang
Ju-Il
JI
Lee
Song Hee
SH
Jang
Sung Key
SK
Ahn
Byung-Yoon
BY
Kim
Yoon Ki
YK
D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000821:virology*; D045744:Cell Line, Tumor; D000242:Cyclic AMP / Q000378:metabolism*; D051786:Cyclic AMP Response Element Modulator / Q000378:metabolism*; D016174:Hepacivirus / Q000502:physiology*; D006801:Humans; D015398:Signal Transduction / Q000502:physiology*; D017361:Viral Nonstructural Proteins / Q000378:metabolism*
C097010:NS2 protein, Hepatitis C virus; D017361:Viral Nonstructural Proteins; D051786:Cyclic AMP Response Element Modulator; D000242:Cyclic AMP