Interferon stimulated gene ISG20 induces an innate immune defense signature in primary human fibroblasts

ISG20 is an interferon-regulated protein that exhibits RNase activity thereby inhibiting the replication of a broad spectrum of RNA viruses. By single cell RNA sequencing we identified ISG20 and several other interferon-regulated proteins as potential restriction factors against human cytomegalovirus (HCMV) since they were highly expressed in a cluster of HCMV resistant cells. Using an siRNA screening strategy we confirmed the antiviral action of ISG20. Overall design: Primary human foreskin fibroblast cells were infected with HCMV (strain AD169) at a multiplicity of infection of 0.4 and harvested at 6 hours post-infection for droplet-based single-cell RNA sequencing.