title: A viral function represses accumulation of transcripts from productive-cycle genes in mouse ganglia latently infected with herpes simplex virus.
abstract: Latent infections of neurons by herpes simplex virus form reservoirs of recurrent viral infections that resist cure. In latently infected neurons, viral gene expression is severely repressed; only the latency-associated transcripts (LATs) are expressed abundantly. Using sensitive reverse transcriptase PCR assays, we analyzed the effects of a deletion mutation in the LAT locus on viral gene expression in latently infected mouse trigeminal ganglia. The deletion mutation, which reduced expression of the major LATs 10(5)-fold, resulted in a approximately 5-fold increase in accumulation of transcripts from the immediate-early gene encoding ICP4, an essential transactivator of viral gene expression. The LAT deletion also resulted in a >10-fold increase in the accumulation of transcripts from the early gene encoding thymidine kinase, whose expression during productive infection stringently depends on ICP4, and positively affected the correlation of the levels of these transcripts with the levels of ICP4 transcripts. We also detected transcripts antisense to ICP4 RNA, which were in substantial excess to ICP4 transcripts in ganglia latently infected with wild-type virus. In contrast to its effects on productive-cycle transcripts, the LAT deletion reduced the accumulation of these antisense transcripts approximately 15-fold. Thus, a viral function associated with the LAT locus represses the accumulation of transcripts from at least two productive-cycle genes in latently infected mouse ganglia. We discuss possible mechanisms and consequences of this repression.
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: S H
authors.initials: SH
authors.lastname: Chen
authors.forename: M F
authors.initials: MF
authors.lastname: Kramer
authors.forename: P A
authors.initials: PA
authors.lastname: Schaffer
authors.forename: D M
authors.initials: DM
authors.lastname: Coen
mesh_terms: D000818:Animals; D004279:DNA, Viral / Q000032:analysis; D005724:Ganglia / Q000821:virology*; D005814:Genes, Viral; D017874:Immediate-Early Proteins / Q000235:genetics*; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism*; D018139:Simplexvirus / Q000235:genetics / Q000502:physiology*; D013937:Thymidine Kinase / Q000235:genetics*; D014775:Virus Activation; D017735:Virus Latency
chemical_list: D004279:DNA, Viral; D017874:Immediate-Early Proteins; D012333:RNA, Messenger; C048925:herpes simplex virus, type 1 protein ICP4; D013937:Thymidine Kinase