This Article Full Text (PDF) Other Versions of this Article: JVI.02443-06v1 81/11/5737    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by JAWORSKA, J. Articles by FLAMAND, L. Search for Related Content PubMed PubMed Citation Articles by JAWORSKA, J. Articles by FLAMAND, L.

 Previous Article  |  Next Article 

J. Virol. doi:10.1128/JVI.02443-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

INHIBITION OF INTERFERON BETA GENE TRANSCRIPTION BY THE HUMAN HERPESVIRUS 6 IMMEDIATE-EARLY 1 PROTEIN

Laboratory of Virology, Rheumatology and Immunology Research Center, CHUQ Research Center and Faculty of Medicine, Laval University, Quebec, Quebec, Canada; Department of Biochemistry, Faculty of Medicine, University of Montreal and CHUM Research Center-Hôpital St-Luc, Montreal, Quebec, Canada

^* To whom correspondence should be addressed. Email: Louis.Flamand{at}crchul.ulaval.ca.

	Abstract

Human Herpesviruses (HHV) are stealth pathogens possessing several decoy or immune evasion mechanisms favoring their persistence within the infected host. Of these viruses, HHV-6 is among the most successful human parasites, establishing life-long infections in nearly 100% of individuals around the world. To better understand this host-pathogen relationship, we determined whether HHV-6 could interfere with the development of the innate antiviral response by affecting interferon (IFN) biosynthesis. Using inducible cell lines and transient transfection assays, we have identified the immediate-early 1 (IE1) protein as a potent inhibitor of ifn- gene expression. IE1 from both HHV-6 variants were capable of suppressing ifn- gene induction. IE1 prevents ifn- gene expression triggered by Sendai virus (SeV) infection, double-stranded RNA (dsRNA) and dsDNA transfection or ectopic expression of ifn- gene activators such as RIG-I, MAVS, TBK-1, IKK or IRF3. While IFN- mRNA stability is not affected, IE1 expressing cells have reduced levels of dimerized IRF3 and nuclear translocated IRF3 in response to activation by TBK-1 or IKK kinases. Using nuclear extracts and gel shift experiments and we could demonstrate that in the presence of IE1, IRF3 does not bind efficiently to the IFN- promoter sequences. Overall these results indicate that the IE1 protein of HHV-6, one of the first viral proteins synthesized upon viral entry, is a potent suppressor of ifn- gene induction and likely contributes to favor the establishment and successful infection of cells by this virus.

This article has been cited by other articles:

• Sullivan, B. M., Coscoy, L. (2008). Downregulation of the T-Cell Receptor Complex and Impairment of T-Cell Activation by Human Herpesvirus 6 U24 Protein. J. Virol. 82: 602-608 [Abstract] [Full Text]  
• Randall, R. E., Goodbourn, S. (2008). Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures. J. Gen. Virol. 89: 1-47 [Abstract] [Full Text]