Grant: CIHR New Investigator

Viruses have evolved strategies to infect host cells and disrupt normal cellular functions while hijacking critical host machineries to express viral genes. However, the host can counteract by using innate antiviral responses to detect and defend against viruses. Revealing the molecular mechanisms between the battle of the virus and host is vital in our fight against clinically relevant viruses. One mechanism that some viruses use is through an IRES. In our cells, molecular machines, called ribosomes, translate our genes into proteins, but some viruses, such as hepatitis C virus and poliovirus, possess an IRES to hijack the ribosome to preferentially express their viral proteins. We need a better understanding of these mechanisms in order to fight viral infections. This proposal will gain insight into these viral IRESs by elucidating the mechanisms by which a unique IRES, found within an insect virus called the cricket paralysis virus (CrPV), can hijack the ribosome. Because the CrPV IRES directly recruits ribosomes without any factors, it provides a simple and powerful model to study IRES functions and will lay the foundation for studying more complex IRESs. Our previous work was seminal in delineating important CrPV IRES functions. Building on this work, we aim: 1) to use innovative techniques to map the specific IRES elements that interact with the ribosome, 2) to determine how the CrPV disrupt cellular functions that leads to IRES activity in Drosophila (fruit fly) cells, and 3) to elucidate the host antiviral responses in Drosophila cells, which have not been fully investigated. Because molecular signals are often conserved, the study of Drosophila antiviral responses is relevant in revealing fundamental virus host interactions in humans. Armed with these interdisciplinary approaches, we will gain valuable into details of viral IRES mechanics, the host disruptions by the CrPV that leads to IRES activity, and the identity of key antiviral responses.