Display omitted •Single cell analyses reveal cell heterogeneity, often masked at population level.•ScRNA-Seq identifies transcriptomic signatures hallmarking distinct cell subsets.•ScRNA-Seq coupled with phenotypic analyses uncovers specific cell subsets.•Subsets with unique molecular signatures are relevant for virus-host interactions.•ScRNA-Seq coupled with phenotypic analyses is a valuable tool in virology. Single-cell analyses allow uncovering cellular heterogeneity, not only per se, but also in response to viral infection. Similarly, single cell transcriptome analyses (scRNA-Seq) can highlight specific signatures, identifying cell subsets with particular phenotypes, which are relevant in the understanding of virus–host interactions.