The IR3 gene of equine herpesvirus type 1: a unique gene regulated by sequences within the intron of the immediate-early gene.
Abstract: The complete nucleotide sequence of the inverted repeat component (IR; 12,776 bp each) of the genome of equine herpesvirus type 1 (EHV-1) has been determined. Transcription analyses have revealed that the EHV-1 IR sequence encodes at least 6 genes. In this report, we present the DNA sequence and transcriptional characterization of a gene (IR3) that maps entirely within the IR sequences. The IR3 open reading frame (ORF) is located between nucleotides (nt) 6123-6411 of the IR sequence and possesses an ORF of 95 amino acids. Interestingly, this ORF does not show homology to any known herpesvirus gene, suggesting that the IR3 gene is unique to EHV-1. Moreover, the location of the IR3 gene between the immediate-early (IR1) gene and the origin of replication is unique in comparison to the IR gene arrangement of other alphaherpesviruses such as herpes simplex virus type 1 and varicella zoster virus. Putative cis-acting elements flanking the IR3 ORF include a TATA box (nt 5648-5652), a GC box (nt 5600-5605), and three polyadenylation signals (nt 6533-6538, 6648-6653, and 6663-6668). Northern blot analyses identified a 1.0 kb mRNA that exhibits characteristics of a late gene of the gamma-1 class. Northern blot, S1 nuclease, and primer extension analyses revealed that transcription of IR3 initiates within the intron of the immediate-early gene (IR1) on the opposite stand of the genome. Thus, the 5' end of IR3 transcript is antisense to the 5' end of the IR1 mRNA and promoter, and IR3 transcription may regulate the expression of IR1 during late times of infection.
Publication Date: 1992-01-01 PubMed ID: 1335300DOI: 10.3109/10425179209034010Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
- Research Support
- U.S. Gov't
- Non-P.H.S.
- Research Support
- U.S. Gov't
- P.H.S.
Summary
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The study details the characterization of a unique gene (IR3) found in the genome sequence of equine herpesvirus type 1 (EHV-1). The uniqueness of the gene is implicated in its structure and its location in the genome—features that differ from other similar viruses.
Genome Analysis of EHV-1
- The paper talks about a comprehensive nucleotide sequence study of the inverted repeat component (IR) of EHV-1. This component has a length of 12,776 base pairs.
- Through transcription analysis, researchers have discovered that at least 6 genes are encoded within this IR sequence.
Introduction to the IR3 Gene
- The focus of the report is the IR3 gene, a gene that is entirely located within the IR sequences.
- The open reading frame (ORF) of IR3, which is the portion of the gene that can potentially be translated into a protein, spans from the 6123rd to the 6411th nucleotides in the IR sequence. This ORF can produce a peptide chain of 95 amino acids.
- Interestingly, the IR3 gene does not show any similarity to known herpesvirus genes, defining its unique nature specific to EHV-1.
Unique Features of IR3
- The location of the IR3 gene in the EHV-1 genome is also unique. Unlike other alphaherpesviruses like herpes simplex virus type 1 and varicella zoster virus, the IR3 gene is found between the immediate-early (IR1) gene and the origin of replication.
- The flanks of the IR3 gene contain potential regions that could regulate its expression, including a TATA box, a GC box, and three polyadenylation signals.
Expression of the IR3 gene
- Northern blot analysis, a technique to detect and isolate RNA sequences, identified an mRNA of 1.0 kilobase in length related to IR3. Properties of this mRNA suggest it is a late gene of the gamma-1 class, expressed later in the viral replication cycle.
- Detailed analysis showed that the debut of IR3 transcription is inside the intron of the immediate-early gene (IR1), on the opposite strand of the genome. As such, the 5′ end of IR3 mRNA is antithesis to the 5′ end of IR1 mRNA and promoter.
- This unique configuration of transcription suggests that the transcription of IR3 might have a feedback role, potentially regulating the expression of IR1 during late times of infection.
Cite This Article
APA
Holden VR, Harty RN, Yalamanchili RR, O'Callaghan DJ.
(1992).
The IR3 gene of equine herpesvirus type 1: a unique gene regulated by sequences within the intron of the immediate-early gene.
DNA Seq, 3(3), 143-152.
https://doi.org/10.3109/10425179209034010 Publication
Researcher Affiliations
- Department of Microbiology and Immunology, Louisiana State University Medical Center, Shreveport 71130-3932.
MeSH Terms
- Animals
- Base Sequence
- Cells, Cultured
- Chromosome Mapping
- DNA, Viral / genetics
- Gene Expression Regulation, Viral
- Genes, Viral
- Herpesvirus 1, Equid / genetics
- Introns
- Molecular Sequence Data
- Repetitive Sequences, Nucleic Acid
Grant Funding
- AI 22001 / NIAID NIH HHS
Citations
This article has been cited 19 times.- Savoret J, Mesnard JM, Gross A, Chazal N. Antisense Transcripts and Antisense Protein: A New Perspective on Human Immunodeficiency Virus Type 1. Front Microbiol 2020;11:625941.
- Shakya AK, O'Callaghan DJ, Kim SK. Comparative Genomic Sequencing and Pathogenic Properties of Equine Herpesvirus 1 KyA and RacL11. Front Vet Sci 2017;4:211.
- 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, 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.
- Ma Y, Wang N, Li M, Gao S, Wang L, Ji Y, Qi Y, He R, Sun Z, Ruan Q. An antisense transcript in the human cytomegalovirus UL87 gene region. Virol J 2011 Nov 11;8:515.
- 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.
- Ahn B, Zhang Y, Osterrieder N, O'Callaghan DJ. Properties of an equine herpesvirus 1 mutant devoid of the internal inverted repeat sequence of the genomic short region. Virology 2011 Feb 20;410(2):327-35.
- Ahn BC, Zhang Y, O'Callaghan DJ. The equine herpesvirus-1 (EHV-1) IR3 transcript downregulates expression of the IE gene and the absence of IR3 gene expression alters EHV-1 biological properties and virulence. Virology 2010 Jul 5;402(2):327-37.
- 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.
- Zhang G, Raghavan B, Kotur M, Cheatham J, Sedmak D, Cook C, Waldman J, Trgovcich J. Antisense transcription in the human cytomegalovirus transcriptome. J Virol 2007 Oct;81(20):11267-81.
- Ahn BC, Breitenbach JE, Kim SK, O'Callaghan DJ. The equine herpesvirus-1 IR3 gene that lies antisense to the sole immediate-early (IE) gene is trans-activated by the IE protein, and is poorly expressed to a protein. Virology 2007 Jun 20;363(1):15-25.
- 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.
- Kim SK, Holden VR, O'Callaghan DJ. The ICP22 protein of equine herpesvirus 1 cooperates with the IE protein to regulate viral gene expression. J Virol 1997 Feb;71(2):1004-12.
- Holden VR, Caughman GB, Zhao Y, Harty RN, O'Callaghan DJ. Identification and characterization of the ICP22 protein of equine herpesvirus 1. J Virol 1994 Jul;68(7):4329-40.
- O'Callaghan DJ, Colle CF 3rd, Flowers CC, Smith RH, Benoit JN, Bigger CA. Identification and initial characterization of the IR6 protein of equine herpesvirus 1. J Virol 1994 Sep;68(9):5351-64.
- Zhao Y, Holden VR, Smith RH, O'Callaghan DJ. Regulatory function of the equine herpesvirus 1 ICP27 gene product. J Virol 1995 May;69(5):2786-93.
- Liu D, Zhao X, Wang X. The Genomic Characterization of Equid Alphaherpesviruses: Structure, Function, and Genetic Similarity. Vet Sci 2025 Mar 3;12(3).
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