Curtis Cai joined the Viral Immunology Systems Program in 2016 to complete an honours project for his undergraduate studies. During the year he studied how HCV populations evolve over the course of an infection using molecular biology and next generation sequencing technologies. Now as a PhD candidate, he has taken on a new perspective to investigate HCV infection- from the host rather than the virus. Chronic HCV infections represent a failure of the host immune system to eliminate the foreign virus. Consequently, HCV populations are able to persist indefinitely in part because of impaired CD8 T cell response (exhaustion). Although years of mouse studies have revealed the defining hallmarks of CD8 T cell exhaustion, there has been limited work translating such findings into a human context using appropriate models. Exhaustion is not only a product of chronic viral infections- immunotherapies such as a checkpoint blockade have demonstrated that CD8 T cell exhaustion also occurs during cancer and that its reversal may lead to successful clinical outcomes.
Curtis leads a project which seeks to using the hepatitis C virus as a model to understand how populations of CD8 T cells develop the exhausted phenotype by following their development and evolution at the early phases of infection. Single cell technologies now offer greater resolution to unravel how individual cells from complex populations change over time. Findings from this project will inform potential HCV vaccines by characterising what constitutes undesirable vaccine-induced CD8 T cell responses. It will also contribute to our knowledge of the basic biology that underpins emerging immunotherapies as they move from the laboratory bench and into the clinic.