Hepatitis C virus (HCV) poses a major threat to human health, causing chronic hepatitis which can then progress into fibrosis, cirrhosis or hepatocellular carcinoma.  In the UK, about 1% of the population is infected with the hepatitis C virus, and hepatitis C induced cirrhosis now comprises the commonest indication for liver transplantation-currently the only treatment for end-stage disease.  Evasion of the immune attack plays a critical role in establishing chronicity and tumor formation.  We are interested in studying how the infected cells become resistant to Fas- and Granzyme-mediated apoptosis induced by the immune cells and also how the infected cells ‘back-kill’ the immune cells by up-regulation of the Fas Ligand.

Virus infections provoke two types of responses: the interferon response and the ER stress response.  The two pathways ‘cross-talk’ and converge at the step of phosphorylation of eIF2a that is crucial for translational regulation.  We are interested in studying how the ER stress response regulates the interferon response during HCV infection and whether the ability to provoke a chronic ER stress response contributes to interferon resistance.  This will provide a novel insight into the mechanism of viral resistance to interferon and help improve the only and yet ineffective treatment for HCV.  We are also interested in studying the role of the ER stress response in the pathogenesis of HCV-associated diseases.

HCV utilises an internal ribosome entry site (IRES) element for translation, in contrast to cap-dependent translation of the majority of cellular proteins.  We are interested in studying the mechanisms of translational control under oxidative stress, as hepatitis C patients very often present elevated levels of oxidants in the blood and liver.  This may lead to a better understanding in the use of anti-oxidants in anti-HCV therapy, which is currently in clinical trials.

Hepatitis C is a clinically important disease affecting 170 million people worldwide and 1% of the UK population. It is caused by the infection of a virus called hepatitis C virus. The virus establishes a life-long chronic infection. About 80% of the infection with hepatitis C virus will develop into chronic hepatitis, of which 20-35% will progress into cirrhosis with a significant number of these leading to liver cancer. We are investigating how the virus can establish chronic infection and how the virus can cause diseases. Our results will provide valuable information in finding ways to interfere with these processes to eliminate the virus and to improved treatment.