Esen Sefik, PhD

Project Title: Elucidating disease mechanisms of dengue virus infection in a humanized liver

Dengue, a viral infection transmitted through the bite of infected mosquitoes, can cause severe disease in humans including severe liver damage such as acute liver failure (ALF) and chronic liver damage (CLD). Dengue virus has four major serotypes. Dengue virus infections are unique in that pre-existing immunity to a serotype can enhance disease against a distinct serotype in a secondary infection, likely because of a phenomenon known as antibody dependent enhancement (ADE). Patients with pre-existing dengue immunity that are infected with a distinct dengue virus serotype from their first infection can develop in severe disease including dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Children who develop DHF and DSS are more likely to present with severe liver disease and ALF. We define dengue virus liver pathogenesis in two complementary humanized mouse models to determine the relative contribution of human macrophage and hepatocytes to acute liver damage in the context of dengue infection. Our mechanistic studies of dengue infection in the liver will reveal new therapeutic targets to mitigate the impact of dengue-mediated ALF and chronic liver inflammation.