The objective of our research is to contribute to a comprehensive understanding of immune control of viral infections, and to use this knowledge to develop novel therapies. Previously, we identified a family of interferon-inducible transmembrane (IFITM) proteins critical to the innate immune response to several highly pathogenic viruses, including SARS coronavirus, influenza A viruses, dengue virus, West Nile virus, Ebola virus, and Marburg viruses. The IFITM protein family has four human paralogs, IFITM1, 2, 3, and 5. As their names indicate, the expression of these proteins is strongly induced by both type I and type II interferons. Our studies demonstrated that IFITM proteins restrict viral replication at the early stage of infection. We also showed that IFITM proteins differentially restrict influenza A viruses and filoviruses. In vivo, IFITM-mediated restriction plays a pivotal role in control of influenza A virus replication. We observed that IFITM knockout mice developed more severe clinical presentations than wild type mice after infection with influenza A viruses. Based on previous IFITM work, our current research focuses on
(1) understanding the mechanisms of IFITM-mediated viral restriction,
(2) investigating the role of IFITM proteins in modulation of adaptive immunity,
(3) determining the importance of human IFITM isoforms in control of viral infections, and
(4) identifying compounds which upregulate the expression of IFITM proteins.
These studies will deepen our knowledge of how innate immunity controls viral infections and how it can modulate adaptive immunity. Furthermore, these studies may provide new approaches for the treatment of viral diseases.