title: The equine herpesvirus-1 (EHV-1) IR3 transcript downregulates expression of the IE gene and the absence of IR3 gene expression alters EHV-1 biological properties and virulence.
abstract: The IR3 transcript of equine herpesvirus-1 (EHV-1) harbors 117 nts antisense to the immediate-early (IE) mRNA, suggesting it plays a regulatory role. Here, we show that the IR3 transcript downregulates IE gene expression and that the absence of IR3 expression altered EHV-1 biological properties and virulence in mice. Reporter assays revealed that the IR3/IE overlapping sequences [IR3(+226/+342)] and an additional IR3(+343/+433) region are necessary for the IR3 RNA to downregulate IE expression. Experiments with the DeltaIR3 EHV-1 showed that the IR3 gene is dispensable for EHV-1 replication. Protein expression of the IE and representative EHV-1 genes was increased in cells infected with DeltaIR3 EHV-1 as compared to that of cells infected with wt EHV-1. The DeltaIR3 EHV-1 exhibited increased virulence in mice as compared to the parent virus. The finding that the IR3 transcript affects IE gene expression extends the role of RNA as a regulatory molecule in alphaherpesvirus infection.
authors.affiliation: Center for Molecular and Tumor Virology, Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, 1501 Kings Highway, P.O. Box 33932, Shreveport, LA 71130-3932, USA.
authors.forename: Byung Chul
authors.initials: BC
authors.lastname: Ahn
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Zhang
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: O'Callaghan
mesh_terms: D000818:Animals; D017353:Gene Deletion; D015967:Gene Expression Regulation, Viral; D017781:Genes, Immediate-Early; D017930:Genes, Reporter; D006566:Herpesviridae Infections / Q000473:pathology / Q000821:virology; D004861:Herpesvirus 1, Equid / Q000502:physiology*; D051379:Mice; D008808:Mice, Inbred CBA; D012333:RNA, Messenger / Q000096:biosynthesis*; D012367:RNA, Viral / Q000096:biosynthesis*; D016019:Survival Analysis; D014158:Transcription, Genetic; D014774:Virulence; D014779:Virus Replication
chemical_list: D012333:RNA, Messenger; D012367:RNA, Viral