The Ras/Raf/MEK Pathway Is Activated By HCV Infection Via Bromodomain Containing Protein 7

Hepatitis C virus (HCV) is a hepatotropic RNA virus belonging to the family Flaviviridae. Its genome was cloned in 1989. HCV is a serious threat to human health, 50-85% HCV infected patients will develop chronic hepatitis, cirrhosis and hepatocellular carcinoma. About 170 million people in the world are affected by hepatitis C virus infection. So far, there is no effective vaccine against it. Nowadays in most countries, the main treatment for HCV is pegylated interferon alpha (PEG-IFN) with ribavirin. Approximately 30% of cancers have constitutive activation of Ras/Raf/MEK pathway, so we want to study whether there is some relationship between HCV replication and this pathway.Based on our previous work, we investigated the process of the activation of Ras/Raf/MEK pathway by HCV in detail, found out the very viral protein that plays the key role in the activation of Ras/Raf/MEK pathway and elucidated the molecular mechanism of this activation. Through this study, we further explaining the molecular mechanism that accouts for the evasion of host antiviral immunology by HCV. Conclusions presented in this thesis are summarized as follows:1. HCV infection leads to the activation of Ras/Raf/MEK pathway, and the viral core and non-structrual proteins play the major roles.2. HCV infection leads to the reduction of BRD7.3. BRD7 inactivates Ras/Raf/MEK pathway in hepatocarcinoma cell.4. The viral NS3, NS5A and NS5B proteins play a major role in the regulation of BRD7 expression.5. HCV regulates BRD7 at transcription level, and the regulation site locates 1000 bp up-stream of BRD7 transcription start site.