Study Of The Relaionship Between Hepatitis C Virus Infection And Interleukin27

Hepatitis C Virus (HCV) causes acute and chronic hepatitis, which often results in the development of liver cirrhosis (LC) and hepatocellular carcinoma (HCC) world-wide. It has been reported that interleukins take important roles in HCV infection. Interleukin-27(IL-27) is a member of the IL-6/IL-12family. It is composed of an IL-12p40-related protein (EBI3) and an IL-12p35-related protein (p28). The receptor complex for IL-27is composed of the signal transducing receptor chains WSX-1and glycoprotein130. IL-27is mainly produced by antigen-presenting cells (APC), in response to infection caused by intracellular pathogens and host immune stimuli. IL-27stimulates naive CD4+T cells to produce interferon-gamma (IFN-y) in synergy with IL-12and plays an important role in bridging innate and adaptive immunities. It is reported that IL-27could inhibit human immunodeficiency virus1(HIV-1), fowl plague virus (FPV) and human influenza virus replications. However, till now, the relationship between HCV infection and IL-27is still not clear.In order to explore the interaction between HCV and IL-27, we investigated the serum IL-27levels from chronic hepatitis C patients and from healthy individuals. The results showed that the IL-27serum level was significantly elevated in the patients. In addition, the in vitro results certified that HCV enhances IL-27p28and EBI3promoter activities. RT-PCR and ELISA results proved that IL-27mRNA and protein expression levels were also elevated by HCV infection. Through the research on signal pathway, NF-κB was proved important for HCV to activate EBI3promoter. And HCV NS3protein was proved to increase EBI3promoter level.In order to explore the influence of IL-27on HCV replication, Huh7.5.1cells were infec6ted by HCV JFH-1produce HCV virus particles in supernatant of cell culture. The HCV RNA in supernatant was examined by fluorescent quantitative RT-PCR. When recombinant IL-27protein was added into the cell culture medium, the capacity of Huh7.51to producing HCV was significantly reduced. The data indicated IL-27could inhibit HCV replication.This research on HCV and IL-27interaction can provide experimental foundation for understanding the molecular mechanism of HCV elevating IL-27expression, theoretical foundation for understanding the host defense mechanism against HCV and also new insights into the development of novel therapeutics against HCV infection.