Research objectives and content
The aim of the project is to investigate whether mutations affecting the CD4+ T helper epitopes of the hepatitis C virus (HCV) core and envelope proteins result in viral escape and relapse following interferon-alpha treatment. The majority of patients with chronic hepatitis C who initially respond to interferon subsequently relapse and the reasons are not clear. Recent data show that a strong cellular immune response to HCV proteins is important for viral clearance. HCV displays a high mutation rate and the role of mutations in altering the immune response is not known. The study will focus on patients with chronic hepatitis C who relapse after interferon treatment The HCV core gene and the hypervariable region will be amplified from paired samples before and after treatment for each patient. Peptides spanning the immunodominant epitopes will be synthesised according to the HCV sequences obtained for the two time points. The proliferative response and cytokine release of CD4+ T helper cells will be investigated against the different peptides to test the hypothesis that emerging mutations aborgate the T cell response and contribute to viral persistence. Training content(objective,benefit and expected impact)
The proposed project will involve training in molecular and immunological techniques ( DNA sequencing, cell cultures and lymphoproliferation assays)and with the education programme of University College London will form an excellent foundation for a future academic career.