While the cytopathic effect (CPE) observed in ISG15−/− after WR infection (0.1 PFU/cell, 24 h) was similar to ISG15+/+ cells (Fig. 2A, upper panels), the CPE in ISG15−/− cells after VVΔE3L infection was markedly increased with respect to that observed in ISG15+/+ cells (Fig. 2A, lower panels). The gene discussed is ISG15; the disease is infection.