129/Sv mice (5 per group) were treated with daily R848 i.p. (2.5 mg/kg) for 14 days. From day 7 onward, one group received oral doses of 15 mg/kg MHV370 b.i.d., one group vehicle. At day 14, both groups were compared to naive 129/Sv mice. Gene expression profiling of blood was performed via amplicon sequencing (Ion AmpliSeq Transcriptome Mouse Gene Expression Kit, Thermo Fisher Scientific). Raw amplicon counts, sample metadata and gene information are provided in tab-separated value (TSV) files counts.tsv, samples.tsv and genes.tsv, respectively. The entire dataset is also provided as a DGEList object saved as an RDS file (dge_unfiltered.rds) that can be explored using R (package edgeR). The respective code for analysis can be found under DOI: 10.5281/zenodo.7575672