Human papillomaviruses cause most cervical cancers, and replicate their genomes in highly differentiated stratified epithelial cells. In normal stratified epithelia, cells exit the cell cycle after leaving the basal layer. In HPV infections, the cells must retain proliferative capacity, because viruses need to use cellular replication factors to reproduce. Marta Melar-New and Laimonis A. Laimins of Northwestern University, Chicago, Ill., show that one of the cellular factors targeted by HPV proteins to allow differentiated cells to remain active in the cell cycle is a cellular microRNA, which plays a big role in regulating proliferation in differentiating cells. In normal epithelia, this microRNA, miR-203, is upregulated upon differentiation. It then inhibits translation of certain transcription regulators that suppress proliferation in differentiating cells. The investigators show that a protein, HPV E7, downregulates miR-203 expression in suprabasal cells, boosting levels of the relevant transcriptional regulators. This, says Laimins, is important for differentiation-dependent HPV replication. Laimins notes that while many viruses encode their own miRNAs, this does not appear to be true for human papillomaviruses. Instead, as this paper shows, HPVs alter expression of cellular microRNAs enable viral replication, a finding which he says may portend similar discoveries in other viruses.