In these studies, recurrent duplications of the K3L gene, which encodes a weak inhibitor of the human innate immune factor Protein Kinase R (PKR; Davies et al., 1992), were identified following serial infections of human cells with a vaccinia strain lacking a strong PKR inhibitor encoded by the E3L gene (ΔE3L; Chang et al., 1992; Beattie et al., 1995). The gene discussed is EIF2AK2; the disease is infection.