HOST TRANSLATION · The translational landscape of virally infected cells

Viruses are completely reliant on the host cell machinery and have evolved many mechanisms to hijack it for their propagation. At the same time our cells have developed defense mechanisms to cope with infections. A key way by which viruses influence host physiology is through interaction with the cellular translation machinery. Not only viruses must co-opt this machinery to translate their own mRNAs, they also have to hinder host defenses that are aimed to inactivate the translation machinery. My research aims to elucidate the complex cellular changes that occur during these virus-cell encounters with a focus on the translation machinery. I plan to concentrate on two major pathogens; a large DNA virus, Human cytomegalovirus (HCMV), and a small RNA virus, Influenza A. Although these viruses are very different, for both of these viruses the global effect of infection on the translation of host genes is still poorly defined. I therefore propose to tackle this important issue by employing a novel deep-sequencing technique termed ribosome profiling, that allows a comprehensive view of translation events. The robustness, scale and accuracy of this analysis will enable us to determine the identity and the relative levels of translation of each host protein during the course of infection and would therefore provide valuable information regarding translational control strategies used by these viruses to reprogram the cellular host translation machinery. I then plan to develop and apply more directed experiment to confirm translational changes and to elucidate their importance to viral replication. These experiments should provide a unique opportunity to understand the underlying changes that occur during infection and to reveal common and unique pathways that viruses use to harness the host translation machinery.