Control of Rta expression critically determines transcription of viral and cellular genes following gammaherpesvirus infection
Hair, J.R Lyons, P.A Smith, K.G.C Efstathiou, S
Hair, J.R
Lyons, P.A
Efstathiou, S
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Alternative Title
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. © 2007 SGM.
Keywords
replication and transcriptional activator protein, unclassified drug, virus protein, animal cell, article, controlled study, gene expression regulation, gene overexpression, gene repression, genetic transcription, Herpes virus, Herpes virus infection, mouse, nonhuman, nucleotide sequence, open reading frame, priority journal, protein expression, transactivation, transcription regulation, virus gene, virus mutant, virus recombinant, virus replication, virus transcription, wild type, Animals, Gene Expression Profiling, Gene Expression Regulation, Viral, Immediate-Early Proteins, Mice, NIH 3T3 Cells, Oligonucleotide Array Sequence Analysis, Rhadinovirus, RNA, Messenger, RNA, Viral, Trans-Activators, Viral Proteins, Virus Replication, Murinae
Source Title
Journal of General Virology
Publisher
Series/Report No.
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Rights
Attribution 4.0 International
Date
2007
DOI
10.1099/vir.0.82548-0
Type
Article