Herpes simplex virus regulatory proteins VP16 and ICP0 counteract an innate intranuclear barrier to viral gene expression.
HSV regulatory proteins VP16 and ICP0 play key roles in launching the lytic program of viral gene expression in most cell types. However, these activation functions are dispensable in U2OS 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 ICP0 in other cells. To distinguish between these possibilities, we examined the phenotypes of somatic cell hybrids formed between U2OS cells and highly restrictive HEL fibroblasts. The U2OS-HEL heterokarya were as non-permissive as HEL cells, a phenotype that could be overcome by providing either VP16 or ICP0 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 ICP0 stimulate viral gene expression at least in part by counteracting this innate antiviral defence mechanism.
Hancock
Meaghan H
MH
Department of Medical Microbiology and Immunology, University of Alberta, 632 Heritage Medical Research Center, Edmonton, Alberta, Canada T6G 2S2. mhancock@ualberta.ca
Corcoran
Jennifer A
JA
Smiley
James R
JR
D002460:Cell Line / Q000276:immunology; D045744:Cell Line, Tumor / Q000276:immunology; D005347:Fibroblasts / Q000276:immunology* / Q000821:virology; D015967:Gene Expression Regulation, Viral; D017405:Herpes Simplex Virus Protein Vmw65 / Q000378:metabolism*; D006801:Humans; D006822:Hybrid Cells / Q000821:virology*; D017874:Immediate-Early Proteins / Q000378:metabolism*; D007113:Immunity, Innate; D018139:Simplexvirus / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication
D017405:Herpes Simplex Virus Protein Vmw65; D017874:Immediate-Early Proteins; D014764:Viral Proteins; D044767:Ubiquitin-Protein Ligases; C051804:Vmw110 protein, Human herpesvirus 1