Shawn Lyons, PhD

Respiratory viruses like RSV (respiratory syncytial virus) and influenza A virus (IAV) rely on human cells to produce the proteins needed for their multiplication. Normally, protein synthesis in cells begins with a factor called eIF4E1. However, our research shows that RSV and IAV bypass eIF4E1 and use a less-studied factor, eIF4E3. This ability may allow these viruses to keep making their proteins even when the cell’s usual protein-making processes are disrupted during stress or infection. This discovery highlights a potential weak spot in how viruses operate. Unlike eIF4E1, eIF4E3 is not impacted by cellular defenses, giving viruses an advantage. We will investigate if other respiratory viruses also exploit eIF4E3 and explore whether blocking eIF4E3 can stop viral multiplication without harming normal cells. These findings could lead to the development of new antiviral treatments targeting eIF4E3 to combat severe respiratory infections.

Update: Viruses like influenza, respiratory syncytial virus (RSV), and human metapneumovirus (HMPV) that attack the respiratory system hijack a cell's protein-making system to replicate themselves. Our research has identified a protein called eIF4E3 as an unexpected factor that viruses depend on in this process, even when infected cells try to shut down protein production as a natural defense against infection. Using advanced gene-editing tools, we confirmed that eIF4E3 is essential for this process. We are now translating these findings in laboratory-grown human lung cells made from stem cells, which closely resemble the cells found in the lungs. Our goal is to determine whether blocking eIF4E3 could stop many different respiratory viruses from replicating, with the goal of targeting eIF4E3 as a novel antiviral strategy to treat a broad spectrum of viruses.