Grant: Catalyst Grant:Infection & Immunity-PHAC-CAID/Hep C Res Init/Biomed/clin stream

In the vast majority of cases, hepatitis C virus (HCV) is able to establish chronic infection that often progresses to end-stage liver disease and even liver cancer. There is no vaccine to prevent hepatitis C and the present treatment is effective in only 50-70% of patients. Hence, the development of new therapies and vaccines is an urgent priority. A potent vaccine should be able to generate efficient immune responses that can limit viral dissemination. This necessitates the stimulation of a specialized blood cell subset known as dendritic cells (DCs), that will be able to induce white blood cells known as T cells that are specific to hepatitis C that are able to kill cells infected with the virus. We have identified a number of sequences within the genome of hepatitis C virus that can stimulate DCs by interacting with a special family of activating molecules known as toll like receptors (TLRs). The goal of this project is to investigate whether these sequences will indeed enhance the function of DCs and their capacity to stimulate specialized T cells against hepatitis C. We will also investigate whether stimulation by these sequences can inhibit hepatitis C virus replication in liver cells. These sequences can then be used in combination with new treatments or vaccines to enhance their capacity to eliminate hepatitis C virus from blood and liver.