Here we investigate PV uncoating and RNA delivery strategies using a combination of cell culture and cell-free assays, which together show that the transfer of PV RNA across endosomal membranes or liposome model membranes is unaffected by high concentrations of RNase A. Furthermore, we present evidence to suggest that the genome of the aphthovirus ERAV is similarly protected from RNase present in the endosome during the infection process, in a mechanism reminiscent of that of the enteroviruses. The gene discussed is RNASE1; the disease is infection.