A novel totivirus alters gene expression and vacuolar morphology in Malassezia cells and induces a TLR3-mediated inflammatory immune response

Most fungal viruses have been identified in plant pathogens, whereas the presence of viral particles in human pathogenic fungi is less well studied. In the present study, we observed extrachromosomal double-stranded RNA (dsRNA) segments in various clinical isolates of Malassezia species. Malassezia is the most dominant fungal genus on the human skin surface, and species in this group are considered to be etiological factors in various skin diseases including dandruff, seborrheic dermatitis, and atopic dermatitis. We identified novel dsRNA segments and our sequencing results revealed that the virus, named MrV40, belongs to the Totiviridae family and contains an additional satellite dsRNA segment encoding a novel protein. The transcriptome of virus-infected M. restricta cells was compared to that of virus-free cells, and the results showed that transcripts involved in ribosomal biosynthesis were down regulated and those involved in energy production and programmed cell death were increased in abundance. Moreover, transmission electron microscopy revealed significantly larger vacuoles for virus-infected M. restricta cells, indicating that MrV40 infection dramatically altered M. restricta physiology. Our analysis also revealed that a viral nucleic acid from MrV40 induces a TLR3-mediated inflammatory immune response in bone marrow-derived dendritic cells (BMDCs) and this result suggests that a viral element contributes to the pathogenesis of Malassezia.