The gamma2 late glycoprotein K promoter of equine herpesvirus 1 is differentially regulated by the IE and EICP0 proteins.
Abstract: The equine herpesvirus 1 immediate-early (IE) phosphoprotein is essential for the activation of transcription from viral early and late promoters and trans-represses its own promoter. Transient-transfection assays showed that the IE protein trans-represses the gamma2 late gK promoter. Gel shift and DNase I footprinting assays demonstrated that the IE protein binds to the gK promoter sequences from -42 to -26 and from -13 to +12 that overlap the transcription initiation site (+1). These results indicated that the IE protein binds to the transcription initiation site of the gK promoter sequences, thereby repressing transcription. On the other hand, the EICP0 protein trans-activates the gamma2 late gK promoter [Bowles, D. E., Holden, V. R., Zhao, Y., and O'Callaghan, D. J. (1997). The ICP0 protein of equine herpesvirus 1 is an early protein that independently transactivates expression of all classes of viral promoters. J. Virol. 71, 4904-4914]. Overall, the EICP0 protein is able to release the gK promoter from the repressive effects of the IE protein. It has not been previously demonstrated that the major immediate-early transcriptional regulator of a herpesvirus represses expression of a late gene during infection.
Copyright 1999 Academic Press.
Publication Date: 1999-04-07 PubMed ID: 10191181DOI: 10.1006/viro.1999.9608Google Scholar: Lookup
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- Journal Article
- Research Support
- U.S. Gov't
- P.H.S.
Summary
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This study explores how the immediate-early (IE) protein phosphoprotein and the EICP0 protein of equine herpesvirus 1 interact with the virus’s gamma2 late glycoprotein K promoter. The researchers found that while the IE protein represses the promoter, EICP0 protein can counteract this repression.
Understanding the Study Focus
- The focus of the research is on the workings of equine herpesvirus 1, specifically how its IE protein and EICP0 protein interact with the gamma2 late glycoprotein K promoter.
- The IE protein plays a crucial role in initiating transcription from the virus’s early and late promoters, and it also suppresses its promoter. This promoter repression helps balance the production of viral proteins.
- The EICP0 protein, on the other hand, can reactivate the gamma2 late gK promoter, working against the repressive action of the IE protein.
- The research thus examines a complex interplay of viral proteins and promoters within the virus’s life cycle.
Methodology and Results
- The researchers used transient-transfection assays to show that the IE protein represses the gamma2 late gK promoter.
- In addition, gel shift and DNase I footprinting assays were used to identify the points at which the IE protein binds to the promoter sequences. It was found to bind to sequences from -42 to -26 and from -13 to +12 that overlap the transcription initiation site.
- These results show that the IE protein immobilizes the transcription initiation site of the gK promoter sequences, which in turn represses transcription.
Significance and Novelty
- This is the first study to demonstrate how a major immediate-early transcriptional regulator of a herpesvirus represses the expression of a late gene during infection.
- The research expands our understanding of how the proteins and promoters of viruses interact, providing possible pathways for future intervention to control or prevent infections.
- The findings are particularly noteworthy considering equine herpesvirus is a significant pathogen in horses, having the potential to cause respiratory disease, neurological disease, and abortion. The study hence helps in developing strategies to combat the virus.
Cite This Article
APA
Kim SK, Bowles DE, O'callaghan DJ.
(1999).
The gamma2 late glycoprotein K promoter of equine herpesvirus 1 is differentially regulated by the IE and EICP0 proteins.
Virology, 256(2), 173-179.
https://doi.org/10.1006/viro.1999.9608 Publication
Researcher Affiliations
- Department of Microbiology and Immunology, Louisiana State University Medical Center, Shreveport, Louisiana, 71130-3932, USA.
MeSH Terms
- Animals
- Binding Sites
- Chloramphenicol O-Acetyltransferase / genetics
- Chloramphenicol O-Acetyltransferase / metabolism
- Equidae
- Gene Expression Regulation, Viral
- Herpesvirus 1, Equid / genetics
- Immediate-Early Proteins / genetics
- Immediate-Early Proteins / metabolism
- Promoter Regions, Genetic
- Repressor Proteins / genetics
- Repressor Proteins / metabolism
- Trans-Activators / genetics
- Trans-Activators / metabolism
- Transcription, Genetic
- Viral Proteins / genetics
- Viral Proteins / metabolism
Grant Funding
- R01 AI022001 / NIAID NIH HHS
- AI-22001 / NIAID NIH HHS
Citations
This article has been cited 16 times.- Oladunni FS, Horohov DW, Chambers TM. EHV-1: A Constant Threat to the Horse Industry. Front Microbiol 2019;10:2668.
- Kim SK, Shakya AK, O'Callaghan DJ. Full trans-activation mediated by the immediate-early protein of equine herpesvirus 1 requires a consensus TATA box, but not its cognate binding sequence. Virus Res 2016 Jan 4;211:222-32.
- Zhang Y, Charvat RA, Kim SK, O'Callaghan DJ. The EHV-1 UL4 protein that tempers viral gene expression interacts with cellular transcription factors. Virology 2014 Jan 20;449:25-34.
- Kim S, Ahn BC, O'Callaghan DJ, Kim SK. The early UL31 gene of equine herpesvirus 1 encodes a single-stranded DNA-binding protein that has a nuclear localization signal sequence at the C-terminus. Virology 2012 Oct 25;432(2):306-15.
- Kim S, Dai G, O'Callaghan DJ, Kim SK. Characterization of cis-acting elements required for autorepression of the equine herpesvirus 1 IE gene. Virus Res 2012 Apr;165(1):52-60.
- Kim SK, Kim S, Dai G, Zhang Y, Ahn BC, O'Callaghan DJ. Identification of functional domains of the IR2 protein of equine herpesvirus 1 required for inhibition of viral gene expression and replication. Virology 2011 Sep 1;417(2):430-42.
- Charvat RA, Breitenbach JE, Ahn B, Zhang Y, O'Callaghan DJ. The UL4 protein of equine herpesvirus 1 is not essential for replication or pathogenesis and inhibits gene expression controlled by viral and heterologous promoters. Virology 2011 Apr 10;412(2):366-77.
- Everett RD, Boutell C, McNair C, Grant L, Orr A. Comparison of the biological and biochemical activities of several members of the alphaherpesvirus ICP0 family of proteins. J Virol 2010 Apr;84(7):3476-87.
- Breitenbach JE, Ebner PD, O'Callaghan DJ. The IR4 auxiliary regulatory protein expands the in vitro host range of equine herpesvirus 1 and is essential for pathogenesis in the murine model. Virology 2009 Jan 20;383(2):188-94.
- Kim SK, Ahn BC, Albrecht RA, O'Callaghan DJ. The unique IR2 protein of equine herpesvirus 1 negatively regulates viral gene expression. J Virol 2006 May;80(10):5041-9.
- Buczynski KA, Kim SK, O'Callaghan DJ. Initial characterization of 17 viruses harboring mutant forms of the immediate-early gene of equine herpesvirus 1. Virus Genes 2005 Oct;31(2):229-39.
- Kim SK, Albrecht RA, O'Callaghan DJ. A negative regulatory element (base pairs -204 to -177) of the EICP0 promoter of equine herpesvirus 1 abolishes the EICP0 protein's trans-activation of its own promoter. J Virol 2004 Nov;78(21):11696-706.
- Kim SK, Jang HK, Albrecht RA, Derbigny WA, Zhang Y, O'Callaghan DJ. Interaction of the equine herpesvirus 1 EICP0 protein with the immediate-early (IE) protein, TFIIB, and TBP may mediate the antagonism between the IE and EICP0 proteins. J Virol 2003 Feb;77(4):2675-85.
- Jang HK, Albrecht RA, Buczynski KA, Kim SK, Derbigny WA, O'Callaghan DJ. Mapping the sequences that mediate interaction of the equine herpesvirus 1 immediate-early protein and human TFIIB. J Virol 2001 Nov;75(21):10219-30.
- Derbigny WA, Kim SK, Caughman GB, O'Callaghan DJ. The EICP22 protein of equine herpesvirus 1 physically interacts with the immediate-early protein and with itself to form dimers and higher-order complexes. J Virol 2000 Feb;74(3):1425-35.
- Bowles DE, Kim SK, O'Callaghan DJ. Characterization of the trans-activation properties of equine herpesvirus 1 EICP0 protein. J Virol 2000 Feb;74(3):1200-8.
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