Aspergillus fumigatus dsRNA virus promotes fungal fitness and pathogenicity in the mammalian host

Aspergillus fumigatus accounts for approximately 65% of all invasive fungal infections in humans, with mortality rates from aspergillosis approaching 50%. Fungal virulence in plant pathogenic fungi can be modulated by viruses that infect fungi, also known as mycoviruses. However, their impact on fungal pathogenesis in mammals has remained largely unexplored. Here, utilizing an A. fumigatus strain naturally infected with the double-stranded RNA virus, A. fumigatus polymycovirus-1M (AfuPmV-1M), we found that the mycovirus confers a substantial survival advantage to the fungus under oxidative stress, heat stress and within the murine lung. Virus-cured fungal strains exhibited reduced conidiation, melanin production and levels of proteins involved in RNA metabolism and stress response, resulting in diminished fitness and virulence in mice. Finally, antiviral treatment during infection reduced AfuPmV-1M viral load, leading to improved survival in infected mice. Taken together, these data suggest that mycoviruses play an important and often underappreciated role as molecular ‘backseat drivers’ in fungal fitness, stress tolerance and disease progression.