The role of CD97 in the host response to infection with influenza A virus (360G-Wellcome-211496_Z_18_Z)

Our risk of dying from infectious disease is determined partly by our genes. We have identified a gene that is associated with risk of severe disease due to influenza in previously healthy adults. Mice lacking this gene also have more severe clinical signs after influenza infection, providing further support for its importance. The protein encoded by the gene is present at high levels on immune cells, but we do not yet fully understand its function. In this study, we will use a range of experimental approaches, integrating data from a genetically modified mouse model and computer-based analysis of next generation sequencing data, to elucidate how this gene functions during influenza to protect against severe disease. We will further study how variations in the gene render some people more susceptible to critical illness, using blood cells from donors carrying different versions of the gene, and by making small artificial changes in the gene in cultured cells. By determining the immune events and molecular pathways involved, the long-term goal is to identify possible new therapeutic targets to improve medical treatment of critically ill patients.