Herpes simplex virus regulatory proteins VP16 and ICP0 counteract an innate intranuclear barrier to viral gene expression

HSV regulatory proteins VP16 and ICPO play key roles in launching the lytic program of viral gene expression in most cell types. However, these activation functions are dispensable in U20S osteosarcoma cells, suggesting that this cell line either expresses an endogenous activator of HSV gene expression or lacks inhibitory mechanisms that are inactivated by VP16 and ICPO in other cells. To distinguish between these possibilities, we examined the phenotypes of somatic cell hybrids formed between U20S cells and highly restrictive HEL fibroblasts. The U20SHEL heterokarya were as non-permissive as HEL cells, a phenotype that could be overcome by providing either VP16 or ICPO in trans. Our data indicate that human fibroblasts contain one or more inhibitory factors that act within the nucleus to limit HSV gene expression and argue that VP16 and ICPO stimulate viral gene expression at least in part by counteracting this innate antiviral defence mechanism. (c) 2006 Elsevier Inc. All rights reserved.