Periodic Reporting for period 4 - GV-FLU (A Genetic View of Influenza Infection) Reporting period: 2020-01-01 to 2021-06-30 Summary of the context and overall objectives of the project Although many factors (molecules or complexes) are known to have a role during the progress of respiratory infection caused by influenza viruses, yet it is unknown where, when, and in what context this role takes place. Revealing the context of activity is key to understanding mechanisms of in vivo infection and how to modulate and prevent susceptibility to infections. In the IGV-FLU project, we proposed to address this challenge through identification of key drivers together with their timing and location of activity. In particular, we exploited the natural genetic variation to collect biological factors, constructed a comprehensive dynamic network model of in vivo infection, and used this model to uncover and validate potential drivers of susceptibility to influenza virus infection. Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far We constructed the integrative network model, and uncovered strong molecular structures of the host response to influenza virus infection that are much more complex than we originally anticipated. Integration of genetics and prior knowledge into this computational model allowed us to characterize novel biological factors that have a critical role during influenza virus infection. We showed the effect of these factors on susceptibility to influenza virus infection, both in human and mouse. Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far) Identification of novel cellular dynamics that have an effect on susceptibility to IAV infection.Identification of key molecular processes that act at the baseline state and have an effect on susceptibility to IAV infection, both in mouse and human.Identification of a general integrative model for the genetic, molecular and cellular determinants of human infections. picture2.png
