title: Herpes simplex virus latent RNA (LAT) is not required for latent infection in the mouse.
abstract: During latent infection by herpes simplex virus (HSV), an abundant latency-associated transcript (LAT) that is antisense to a predominant viral alpha gene (ICP0) is found localized in the nucleus of sensory neurons. We disrupted both copies of the LAT gene in the HSV-1 genome by insertion of the Escherichia coli lacZ gene under LAT promoter control. The resulting recombinant virus, RH142, does not express any detectable LAT in either latently or productively infected cells, although beta-galactosidase expression is readily detectable in sensory neurons of latently infected mice. Expression was first detectable 3 days postinoculation and continued at approximately the same level for the entire experimental period (56 days). beta-Galactosidase expression was not detectable at any time during RH142 replication in Vero cells. Thus, the kinetics of expression and cell-type specificity of the LAT gene are distinct from other HSV-1 genes that are expressed during productive growth. When latently infected trigeminal ganglia were explanted, RH142 reactivated from latency with the kinetics and an efficiency indistinguishable from the parental wild-type virus. These studies argue against any possible antisense regulatory mechanism of LAT in the regulation of viral gene expression or any role of LAT-encoded protein during the establishment or maintenance of latency in the mouse.
authors.affiliation: Department of Microbiology and Immunology, Stanford University School of Medicine, CA 94305.
authors.forename: D Y
authors.initials: DY
authors.lastname: Ho
authors.forename: E S
authors.initials: ES
authors.lastname: Mocarski
mesh_terms: D000818:Animals; D005814:Genes, Viral; D006561:Herpes Simplex / Q000382:microbiology*; D051379:Mice; D010957:Plasmids; D015347:RNA Probes; D012367:RNA, Viral / Q000235:genetics* / Q000302:isolation & purification; D015183:Restriction Mapping; D018139:Simplexvirus / Q000235:genetics / Q000472:pathogenicity*; D014162:Transfection
chemical_list: D015347:RNA Probes; D012367:RNA, Viral