Aspergillus  fumigatus  AF293 congenic strain. Cyclohexamide-cured and a re-infected strains, and Ribavirin-cured strain.
Fungal pathogens pose a significant threat to global health. Aspergillus fumigatus accounts for approximately 65% of all invasive fungal infections in humans, with mortality rates from aspergillosis reaching nearly 50%. Fungal virulence in plant pathogenic fungi can be modified by mycoviruses, viruses that infect fungi. However, their impact on fungal pathogenesis in mammals has remained largely unexplored. Here, utilizing an A. fumigatus strain naturally infected with Aspergillus fumigatus polymycovirus-1M (AfuPmV-1M), we found that the mycovirus confers a significant survival advantage to the fungus under conditions of oxidative stress, heat stress, and within the murine lung. Thus, AfuPmV-1M modulates fungal fitness, resulting in increased virulence and the progression of exacerbated fungal disease. Moreover, antiviral treatment reverses the exacerbated virus-mediated virulence, representing a promising "antipathogenicity" therapy against virus-bearing pathogenic fungi. Taken together, these data suggest that mycoviruses play a significant role as "backseat drivers" in human fungal diseases, presenting critical clinical implications.