Virulence evolution of Japanese encephalitis virus along the axis of pigs, mosquitoes, and humans in Asia

The nature of unceasingly mutating RNA viruses drives the evolution of virulence, which determines the consequence of zoonotic virus infections.

The zoonotic infections of Japanese encephalitis virus (JEV) from pigs and via mosquitoes to humans, causes most serious human acute viral meningitis in Asia.

The recent replacement of JEV genotype III with genotype I highlights the alteration of JE epidemiology with ill-understood questions.

How JEV evolves along the host axis and especially how these changes are linked to the virulence evolution, are the key scientific questions for understanding the epidemiology of JE, which will provide valuable knowledge for updating the JE vaccine program for animals and humans.

To this end, the proposal aims to decipher JEV virulence evolution features by epidemiological and phylogenomic studies of JEV along its transmission chains between pigs, mosquitoes, and humans in Vietnam and Cambodia.

Furthermore, we will employ omics approaches and application of susceptible cell, mosquito, and mouse models to evaluate the mutations of interest and their association with viral virulence.

Additionally, based on the theory of convergent evolution in RNA viruses, we will establish laboratory infection cycles of JEV to identify the key mutations that might emerge in future outbreaks.

Altogether, this project will yield comprehensive knowledge on virulence evolution of JEV, which will help reducing JE disease burden in the southeast Asia.