Since its identification in 1989, the hepatitis C virus (HCV) has infected over 170 million people worldwide with 38 million people in China alone, and is a causative agent of liver cirrhosis and hepatocellular malignancy. This highly mutable virus gives rise to hypervariable replicates which manages to outpace the host’s immunological defence. As a consequence, most HCV infected people develop chronic liver disease. Current mainstream antiviral therapies exhibit a 50% efficacy towards patients treated and is often poorly tolerated. In addition, genotypic HCV heterogeneity has so far thwarted attempts to develop vaccines targeting HCV. Recent development of an HCV cell culture system for full and efficient virion replication has been instrumental towards basic research to further our understanding of the entire HCV life-cycle, but we are still outmanoeuvred by HCV persistence in the liver...Fork head box P3+ (FOXP3+) CD4+ CD25+ regulatory T cells (Treg) suppress T cell effector (Teffector) function and are important in limiting autoimmunity, play a role during viral infection, and are rapidly recruited to the liver of transgenic mice with immunosuppressive properties towards peripherally or locally activated CD8+ T cells. In vitro analysis has revealed that HCV specific FOXP3+ CD4+ CD25+ T cells can suppress HCV-specific CD8+ T cells, and FOXP3+ CD4+ CD25+ T cells have been shown to recognise the same HCV antigens as CD4+ T-helper cells. Concordantly, reports have shown that the proportion of intrahepatic FOXP3+ CD4+ T cells is increased during persistent HCV infection, and observation of HCV specific CD4+ CD25+ T cells further exemplifies the potential role of Tregs in defining local intrahepatic environments in which chronic infection becomes permissive. However, what remains undefined, are the molecular mechanisms which cause this break of immune homeostasis to permit chronic infection...Broadly, my aim is to explore the molecular determinants which induce Treg interactions with Teffector, DC, or host cell regulation under different environmental stimuli, and to relate this to immune/hepatic cell interactions during HCV infection. These studies will provide innovative clues to ways of manipulating the host immune system in order to tip the balance from chronic HCV permissive environments towards viral clearance, or provide future therapeutic direction for the development of FOXP3-specfic targeted drugs. ..We have already taken part in an exciting investigation into the immunological profiles of a unique cohort of HCV infected patients in China. The blood samples have been analysed by various members of our team and is under constant investigation to elucidate the factors required for host immunity toward HCV.