Grant: Joint Canada-Israel Health Research Program

The ability of viruses to rapidly change is key to their success, allowing them to quickly adapt to new hosts and environments. This ability is what allows viruses to jump between different species as well as to replicate in extremely different environments. Understanding how viruses evolve to efficiently infect in new environments as well as revealing the barriers and limitations to this capacity are thus important to our ability to predict emerging threats and to design novel therapeutic interventions. We here focus on a biomedically important group of viruses - the flaviviruses, that include many human pathogens such as Dengue virus and Zika virus, that infect millions of humans across the world every year, and causing widespread mortality and morbidity. These pathogens are transmitted to humans from ticks and insects, and they are thus able to replicate in two extremely different host environments. These pathogenic viruses have closely-related viruses that can only replicate in insects. We will investigate a viral protein that is important for successful replication in human cells. This protein exists in all flaviviruses, including both pathogenic viruses that transfer from arthropods to humans as well as insect-specific flaviviruses. By comparing the interactions formed between human proteins and variants of this protein from a diverse set of flaviviruses, we will be able to decipher how pathogenic arthropod-borne flaviviruses are able to efficiently infect human cells. We will also study which interactions these viruses form with mosquito proteins, to understand the full set of interactions and functions that these viral proteins perform. Our work will find weak points in flavivirus genomes that are important for their ability to infect their human hosts. These findings may provide candidates for antiviral therapeutics and can assist in predicting emergence of new viral strains.