HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Free via Open Access: OA OA Free Full Text Full Text (PDF) Supplementary Material Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Hair, J. R. Articles by Efstathiou, S. Search for Related Content PubMed PubMed Citation Articles by Hair, J. R. Articles by Efstathiou, S. Agricola Articles by Hair, J. R. Articles by Efstathiou, S.

Control of Rta expression critically determines transcription of viral and cellular genes following gammaherpesvirus infection

¹ Cambridge Institute for Medical Research and the Department of Medicine, Wellcome Trust/MRC Building, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2XY, UK
² Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK
³ 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

Correspondence
Stacey Efstathiou
se{at}mole.bio.cam.ac.uk

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.

Supplementary material is available with the online version of this paper.