Grant: Project Grant

All viruses go through an important stage during their life cycle called translation where viral proteins are synthesized from a viral RNA. Some viruses such as poliovirus and Hepatitis C virus use a translation mechanism called an Internal Ribosome Entry Site or IRES for expressing their proteins. This IRES mechanism is not only important for viruses but also for cellular genes, including those involved in cancer. Therefore, elucidating IRES mechanisms is crucial for understanding a fundamental process of gene expression. Currently, IRES mechanisms are poorly understood. To gain insight, we will characterize a novel IRES mechanism found in an insect virus, called the Cricket Paralysis virus. Using biochemical techniques, we will identify how this IRES interacts with and hijacks the host cell's machinery. Furthermore, we found that this IRES can direct translation of two overlapping genes thus producing a hidden viral protein. We will explore how this novel mechanism increases the coding capacity of a viral genome (recoding) using a combination of biochemical, molecular and virological approaches. Numerous viruses such as HIV and coronavirus (i.e. SARS) use recoding mechanisms to expand coding capacity. Thus, this proposal will not only shed light into the biochemical mechanisms underlying this novel viral IRES recoding mechanism but also provide a unique and powerful model for understanding how other viral IRES and recoding mechanisms work. Understanding these fundamental mechanisms are important for human health; it provides a framework for understanding viruses that infect humans and gains useful knowledge that may reveal novel targets for antiviral therapy.