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

At 24 h post infection, 246 genes were upregulated and 13 genes were downregulated. All the genes from the 6-h time point are included in the 24-h-upregulated genes (see Figures 2A and 2B) . Comparisons with the pan-species database of IFN-triggered transcriptomes (Shaw et al., 2017) identified conserved additional ISGs (besides the ones mentioned for the 6-h time point) such as, e.g., ADAR, BST2, various GBPs, HERC6, IFITM 2 and 3, IRF9, PARP12, PML, RSAD2, TRIM22, SOCS1, STAT1, STAT2, or ZBP1. SAMHD1, by contrast, was recently described as being IRF3 dependent in human, monkey, and porcine cells (Yang et al., 2016) . Among the late virus responders were also more unusual genes such as CSF2 or NEURL3. Both are weakly IFN stimulated in Rattus norvegicus but not in any other mammalian species (Shaw et al., 2017) . In M. daubentonii, CSF2 is exclusively virus inducible (see below) and NEURL3 is strongly virus as well as (weakly) IFN inducible. The genes upregulated at this later time point were functionally more diversified than the 6-h ones, as they promote adaptive immunity, apoptosis, and also RNA polymerase II activity, besides the innate immune response ( Figure S4A , lower panel). The genes downregulated at 24 h post infection were mostly involved in carbohydrate metabolism and protein transport.