title: Control of Rta expression critically determines transcription of viral and cellular genes following gammaherpesvirus infection.
abstract: The replication and transcriptional activator (Rta), encoded by ORF50 of gammaherpesviruses, initiates the lytic cycle of gene expression; therefore understanding the impact of Rta on viral and cellular gene expression is key to elucidating the transcriptional events governing productive infection and reactivation from latency. To this end, the impact of altering Rta transcription on viral and cellular gene expression was studied in the context of a whole virus infection. Recombinant murine gammaherpesvirus (MHV)-68 engineered to overexpress Rta greatly accelerated expression of specific lytic cycle ORFs, but repressed transcription of the major latency gene, ORF73. Increased expression of Rta accelerated the dysregulation in transcription of specific cellular genes when compared with cells infected with wild-type and revertant viruses. A subset of cellular genes was dysregulated only in cells infected with Rta-overexpressing virus, and never in those infected with non-overexpressing viruses. These data highlight the critical role of Rta abundance in governing viral and cellular gene transcription, and demonstrate the importance of understanding how the relative expression of ORF50 during the virus life cycle impacts on these processes.
authors.affiliation: Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.|Cambridge Institute for Medical Research and the Department of Medicine, Wellcome Trust/MRC Building, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2XY, UK.
authors.forename: James R
authors.initials: JR
authors.lastname: Hair
authors.affiliation: Juvenile Diabetes Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research and the Department of Medicine, Wellcome Trust/MRC Building, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2XY, UK.|Cambridge Institute for Medical Research and the Department of Medicine, Wellcome Trust/MRC Building, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2XY, UK.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Lyons
authors.affiliation: Cambridge Institute for Medical Research and the Department of Medicine, Wellcome Trust/MRC Building, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2XY, UK.
authors.forename: Kenneth G C
authors.initials: KGC
authors.lastname: Smith
authors.affiliation: Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
authors.forename: Stacey
authors.initials: S
authors.lastname: Efstathiou
mesh_terms: D000818:Animals; D020869:Gene Expression Profiling; D015967:Gene Expression Regulation, Viral; D017874:Immediate-Early Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D041681:NIH 3T3 Cells; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012367:RNA, Viral / Q000096:biosynthesis / Q000235:genetics; D018144:Rhadinovirus / Q000235:genetics / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D014764:Viral Proteins / Q000235:genetics / Q000502:physiology*; D014779:Virus Replication
chemical_list: D017874:Immediate-Early Proteins; D012333:RNA, Messenger; D012367:RNA, Viral; D015534:Trans-Activators; D014764:Viral Proteins