Stress Responses and the Control of Influenza Virus Infection

All viruses depend on host cell machinery to support viral replication and spread. Influenza virus messenger RNAs are structurally indistinguishable from host cell mRNAs, allowing them to be efficiently translated by the host machinery. This dependence on host cell translation machinery allows for efficient viral gene expression, but it also places the virus in jeopardy because host cells have evolved mechanisms to sense viral infection and rapidly arrest translation. Thus, stress induced translation arrest represents an important form of antiviral host defense that influenza viruses must overcome to make proteins and replicate. Our laboratory studies cellular antiviral stress responses and how viruses undermine these responses. We have discovered that influenza virus infection can be detected by host cell stress responses, and that these stress responses block translation and viral replication. However, we have also discovered that influenza virus makes three proteins that mitigate stress and allow translation, and replication, to continue. Our research is dedicated to better understanding the interaction between these virus proteins and the host antiviral stress responses, in order to define targets for therapeutic intervention.