The evolution of host-flavivirus interactions and their impact on viral pathogenesis and host response

The ability of viruses to rapidly change is key to their success, allowing them to quickly adapt to new hosts 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 important to predicting emerging threats and to designing novel therapeutic interventions. This project focuses on the flaviviruses, a group that includes many human pathogens such as the dengue virus and the zika virus. These viruses infect millions of humans across the world every year, causing widespread mortality and morbidity, especially in developing countries. These pathogens are transmitted to humans from ticks and insects, and they are thus able to replicate in two extremely different host environments. The molecular mechanisms that affect the potential of flaviviruses to shift hosts and become a new human pathogen remain poorly understood. An important factor contributing to virus replication within a given host is the virus'Äô capacity to inhibit intracellular host defences by direct interactions with the host proteins involved in innate immune responses. A non-structural protein 5 (NS5) is common to all flaviviruses and is believed to be important for modulating host innate immune response. This project aims to investigate the hypothesis that NS5 diversity among flaviviruses is central to host modulation and virus spread. The project will create a comprehensive map of its interactions with human and mosquito proteins and study how host-flavivirus interactions impact on host immune processes. This project was selected for funding during the second research competition of the Joint Canada-Israel Health Research Program 'Äì Phase II (Communicable Diseases). The program is a partnership between IDRC, the Canadian Institutes of Health Research, the Israel Science Foundation and the Azrieli Foundation.