Flaviviruses such as Japanese encephalitis and West Nile virus, hijack axonal transport mechanisms to spread throughout the hosts nervous system. They can infect our neurons causing severe and often fatal damage.
During viral infections, neurons activate self-destruction of their long processes called axons. Recently it has been identified that this process occurs through the action of Sterile-alpha and TIR motif containing 1 (SARM1). SARM1 has a unique ability to digest the essential energy molecule NAD+ initiating a cascade of events, committing the axon to degeneration. However, its role during viral neuro-invasion and as an innate immune molecule is not fully understood.
This project uses an ex-vivo model of primary embryonic mouse neural cultures to investigate the role of SARM1 in flavivirus induced axon degeneration. It has been identified that flavivirus infection in neurons activates axonal degeneration partially mediated by SARM1 protein. Further evidence suggests that astrocytes, key neuronal support cells in the nervous system, may also have a role in the activation of this pathway.
This project aims to identify how SARM1 and astrocytes contribute to axon degeneration across multiple strains of flaviviruses. Gaining this knowledge will significantly contribute to understanding the neuropathology induced by flavivirus infection as well as the complex role of SARM1 gene in viral infections and neurodegenerative diseases.