Antagonistic Activity Against Innate Immunity Determines Virulence in Mammalian Bornaviruses

Variegated squirrel bornavirus 1 (VSBV-1) is a lethal emerging disease that has been discovered in privately owned and zoo squirrels, but its pathogenicity as a zoonotic pathogen remains uncertain. To better understand VSBV-1 virulence, we investigated its virological properties and developed a recombinant virus with Borna disease virus 1 (BoDV-1), a classic mammalian bornavirus. Our study revealed that the recombinant BoDV-1, carrying the VSBV-1 X/P sequence, had a 100% lethality rate and was significantly more pathogenic in adult rats than the wild-type BoDV-1. These findings not only enhance our understanding of VSBV-1 virulence, but also provide crucial insights for the development of vaccines and therapeutics against emerging bornaviruses.