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

Minji Park; Yong-Joon Cho; Donggyu Kim; Chul-Su Yang; Shi Mun Lee; Thomas L. Dawson; Satoshi Nakamizo; Kenji Kabashima; Yang Won Lee; Won Hee Jung

The overall dysregulation of primary metabolism may disturb the normal cell physiology in The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2019.12.17.880526 doi: bioRxiv preprint fungal cells, respectively. Moreover, MRET_0103 (FAS-associated factor), which is involved 272 in Fas-induced cell death, was found to be strongly upregulated (8.80-fold) in the presence of 273 the virus within the fungal host (43). It is well-known that programmed cell death is triggered showed significantly increased production of all cytokines tested. However, a relatively small 307 increase was observed in BMDCs treated with purified capsid protein, suggesting that the 308 MrV40 capsid contributes to cytokine production, but the contribution of the protein is 309 marginal (Fig. 7B) . Cytokine profiles were also measured in homozygous TLR3 knockout 310 mice, as our observations suggested a connection between TLR3 and cytokine production 311 upon MrV40 treatment. As shown in Fig. 7B , compared to wild-type BMDCs, cytokine levels 312 in BMDCs isolated from TLR3 knockout mice were not significantly altered. These data 313 suggest that increased production of the cytokines TNF-α, IL-6, IL-10, IFN-α, and IFN-γ in 314 response to MrV40 was TLR3-dependent in BMDCs. Our data also showed that the MrV40 315 capsid proteins caused a marginal increase in cytokine expression in both wild-type and TLR3 316 knockout BMDCs, indicating that the response to the viral capsid is TLR3-independent. The copyright holder for this preprint (which was not peer-reviewed) is the . https: //doi.org/10.1101 //doi.org/10. /2019 The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10. 1101 /2019 MrV-Ls were clustered into three clades (clade â… , â…¡, and â…¢