Grant: Master's Award: Canada Graduate Scholarships

Hepatitis C virus (HCV) is an RNA virus that causes ~71 million chronic HCV infections globally. HCV can be transmitted via bloodborne routes, such as from contaminated medical devices, intravenous drug use, sexual activity, and during childbirth. Although some individuals naturally clear the virus, 60% to 80% of people develop chronic HCV infection. Unfortunately, chronic HCV infection puts these individuals at risk for developing liver disease and an aggressive form of liver cancer, called hepatocellular carcinoma (HCC). According to the World Health Organization, more than 290,000 people die annually due to HCV-related liver damage and HCC. Host immune receptors such as retinoic inducible gene 1 (RIG-I) can detect RNA viral infection and stimulate the production of antiviral molecules called interferons (IFNs). These IFNs can establish antiviral states within cells which can inhibit HCV viral replication and prevent chronic infection. A cellular factor called cyclophilin A (CypA) plays an important role in regulating these RIG-I and IFN signaling pathways at various levels to induce this antiviral state. Generally, HCV can avoid these immune responses, in part by using a viral protein component called non-structural protein 5A (NS5A). We hypothesize that NS5A binds to CypA, preventing it from contributing to RIG-I and IFN responses. This research aims to address the involvement of CypA in the IFN response and the role of CypA in the HCV NS5A-mediated evasion of the IFN response. Since this immune evasion can foster an environment that promotes chronic HCV infection, which is associated with liver inflammation and HCC progression, these research findings may help to inform development of therapeutics which prevent HCV-related liver damage and HCC development.