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.
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.
Ahn
Byung Chul
BC
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.
Zhang
Yunfei
Y
O'Callaghan
Dennis J
DJ
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
D012333:RNA, Messenger; D012367:RNA, Viral