a, Top, representative images of SKH-1 mice with no evidence of disease following infection (immune) and with visible warts after back-skin infection with MmuPV1 (non-immune). Bottom, MmuPV1 L2 RNA ISH of skin from an immune and a non-immune mouse, collected three weeks after infection with MmuPV1, to detect viral activity in the normal skin and the MmuPV1-driven wart. Insets highlight the active virus in the normal skin of the immune mouse and the wart of the non-immune mouse. b, Macroscopic images of the SKH-1 mice three months after MmuPV1 back-skin infection. SKH-1 mice with spontaneous immunity to the virus (no wart) were treated once with an immunosuppressive dose of UVB (300 mJ cm−2); images of the mice three weeks after UV treatment are shown. Arrows point to the newly developed warts on the UV-treated skin. c, Histological images of a wart (yellow circle), stained with H&E and MmuPV1 RNA ISH. The magnified inset highlights MmuPV1-induced cytopathic changes in the H&E image and confluent positive MmuPV1 RNA ISH signals in the wart. d, Macroscopic images of MmuPV1-infected SKH-1 mice that continued to have warts (yellow arrows) before MmuPV1 vaccination, four weeks after vaccination and at the completion of the UV carcinogenesis protocol. The nine wart-bearing mice were treated with MmuPV1 live virus particles intraperitoneally three times over two weeks. Four weeks later, the mice underwent the UV carcinogenesis protocol. Mice with acquired antiviral immunity (n = 5) are compared with non-immune mice that have persistent warts (n = 4). e, Skin tumour burden in vaccinated immune (n = 5) and non-immune (n = 4) mice treated with the UV carcinogenesis protocol. In mice with a confluent pattern of skin tumours, counts represent the individual lesions before their coalescence. Two-tailed Mann–Whitney U test; data are mean ± s.d. f, Representative images of CD3/CD45-stained skin from MmuPV1/DMBA–UV SKH-1 mice compared with sham/DMBA–UV controls at the completion of the UV carcinogenesis protocol. Arrows indicate T cells in the epidermis; dashed lines highlight the epidermal basement membrane. g–i, Skin-infiltrating total CD45+ leukocytes (g), CD3+CD45+ T cells (h) and CD3−CD45+ leukocytes (i) quantified in CD3/CD45-stained skin sections of MmuPV1/DMBA–UV (n = 10) and sham/DMBA–UV (n = 9) SKH-1 mice across ten randomly selected HPF images of each skin sample and averaged across the mice in each group. Each dot represents one high-power image. Note the trend towards an increase in T cells and a decrease in CD3− inflammatory cells in MmuPV1/DMBA–UV skin compared with sham/DMBA–UV control. j, Representative images of CD3/CD45-stained cells in the skin tumours of MmuPV1/DMBA–UV SKH-1 mice compared with sham/DMBA–UV controls at the completion of the UV carcinogenesis protocol. Magnified insets highlight the immune cells in the tumour parenchyma. k–m, Tumour-infiltrating total CD45+ leukocytes (k), CD3+CD45+ T cells (l) and CD3−CD45+ leukocytes (m) quantified in CD3/CD45-stained sections of MmuPV1/DMBA–UV and sham/DMBA–UV SKH-1 skin tumours across HPF images of each tumour and averaged across the mice in each group (n = 12 early skin tumours per group). Each dot represents one high-power image. Stained cells were counted blindly. Two-tailed unpaired t-test; data are mean + s.d. (g–i, k–m). Scale bars, mouse, 1 cm (a, b, d); tissue, 100 μm (a, c, f, j). Source data