Function and specificity of T cells in persistent virus infection.

The immune system's CD8+ and CD4+ T cells are failing to clear hepatitis C virus (HCV) from the liver, and this project will dissect exactly which subsets of these cells are malfunctioning and why. This matters because persistent HCV infection is a major cause of chronic liver disease, cirrhosis, and cancer. Current treatments can cure the virus, but they do not restore a fully functional immune response, leaving patients vulnerable to reinfection and long-term liver damage. The fundamental gap is that scientists do not understand which specific T cell subsets are protective and which are exhausted or dysfunctional during chronic infection. If this research succeeds, it could identify precise T cell populations—marked by the surface protein CD161—that are capable of clearing infected liver cells. This would provide a roadmap for designing vaccines or immunotherapies that train the immune system to mount a durable, effective response against HCV. In the longer term, the same principles could apply to other persistent viruses, such as hepatitis B or HIV, where T cell exhaustion is also a barrier to immunity. This is primarily fundamental science. It seeks a mechanistic understanding of T cell behaviour in a persistent infection, not an immediate clinical product. However, similar fundamental work on T cell exhaustion in chronic viral infections has already led to checkpoint inhibitor therapies that revolutionised cancer treatment.