Virus- and Interferon Alpha-Induced Transcriptomes of Cells from the Microbat Myotis daubentonii

Hölzer, Martin; Schoen, Andreas; Wulle, Julia; Müller, Marcel A.; Drosten, Christian; Marz, Manja; Weber, Friedemann

Bats, which comprise about 20% of all living mammal species, have recently come into the focus of virus and innate immunity research. However, the group of ''bats'' is very heterogeneous and encompasses both Yinpterochiroptera and Yangochiroptera, which have diverged since approximately 60 million years (Teeling et al., 2018) . For Yangochiroptera microbats, in contrast to megabats of the Yinpterochiroptera suborder, the IFN system is only poorly characterized. Here, we presented the time-dependent transcriptional profiles of M. daubentonii cells infected with a strong IFN inducer virus or treated with IFN. Our data revealed virus-triggered genes (CCL4, IFNL3, CH25H, STEAP4) that are not regulated by IFN itself, as well as the presence of multiple paralogs of directly antiviral ISGs such as Mx and BST2. CCL4 and IFNL3 attract immune cells and enhance local antiviral activity, respectively, and Mx, BST2, and CH25H are broad-spectrum virus inhibitors. Although our data are derived from a single cell line and may not be entirely generalizable, our analysis indicates that the Yangochiroptera microbat IFN system may exhibit features not observed for megabats or humans (STEAP4 as virus-response gene, at least 3 BST2 paralogs). Moreover, we report the absence of a series of megabat ISGs (EMC2, FILIP1, Figure 5 . RT-qPCR Confirmation of Virus-Only Response Genes Human A549 and M. daubentonii MyDauNi cells, treated or not with Ruxolitinib, were incubated with 1,000 U/ml IFN-a or infected with Clone 13 (MOI 5) for 6 or 24 h, respectively. Expression of IFNB1, CCL4, IFNL2/3 (A549)/IFNL3 (MyDauNi), CH25H, and STEAP4 were monitored by RT-qPCR. The graphs show the fold induction over mock, for the respective time point, with mean values and standard deviations from three independent replicates.