Defective cell integrity occurs during response to viral skin infections. (A) Representative skin disease, 7 d after epicutaneous HSV infection of WT or Dock8-deficient (KO) mice. Blue arrowheads, primary infection sites. Red arrowhead, blistering along infected dermatome. Orange arrowhead, blistering with skin necrosis. (B) Daily scoring of disease severity after acute HSV infection of WT (black) or KO (red) mice. (C) Kaplan-Meier survival curves for the mice from (B). (D) Two-photon imaging of Dock8-deficient cpm (green) or Dock8-replete T cells from WT gBT-I mice (red) migrating in the dermis, 7 d after adoptive cotransfer into WT recipient mice and HSV infection. White arrow, fragmentation. Frames show time elapsed (minutes). (E) Proportions elongated of the cotransferred T cells in D. Bars, 15 µm. B shows means ± SEM, with a total of 10 or 14 mice per group from two experiments. E shows means ± SD, where data were pooled from six mice from two experiments. Wilcoxon matched-pairs signed rank sum test (two-tailed) was performed for B, log-rank (Mantel-Cox) test for C, unpaired two-tailed Student’s t test for E. Statistical significance indicated by *, P < 0.05; ***, P < 0.001.