Grant: Project Grant

Cells respond to a virus infection by inducing a set of proteins that function to block virus replication and spread. Much is known about how cells recognize the accumulation of specific virus components within a cell. We previously discovered that in response to all enveloped viruses, cells can also recognize the general entry process, following disruption of the cell membrane. We identified an essential cellular factor, IRF3, that is activated and induces a non-specific anti-viral response that protects the cell against diverse viruses, by targeting conserved viral processes. IRF3 is emerging as a key player in recognizing and responding to many types of cellular stress, suggesting that entry of virus particles is likely sensed as a host stress response. Here, we propose to understand how the virus entry process activates this stress response, and identify key events and pathways. Findings will enable the development of novel, generic antiviral therapies capable of protecting against new, emerging viruses. Moreover, as IRF3 is implicated in a myriad of seemingly unrelated diseases, understanding its activation and function is of clinical importance.