The UL4 protein of equine herpesvirus 1 is not essential for replication or pathogenesis and inhibits gene expression controlled by viral and heterologous promoters.
Abstract: Defective interfering particles (DIP) of equine herpesvirus 1 (EHV-1) inhibit standard virus replication and mediate persistent infection. The DIP genome is comprised of only three genes: UL3, UL4, and a hybrid gene composed of portions of the IR4 (EICP22) and UL5 (EICP27) genes. The hybrid gene is important for DIP interference, but the function(s) of the UL3 and UL4 genes are unknown. Here, we show that UL4 is an early gene activated solely by the immediate early protein. The UL4 protein (UL4P) was detected at 4hours post-infection, was localized throughout the nucleus and cytoplasm, and was not present in purified virions. EHV-1 lacking UL4P expression was infectious and displayed cell tropism and pathogenic properties in the mouse model similar to those of parental and revertant viruses. Reporter assays demonstrated that the UL4P has a broad inhibitory function, suggesting a potential role in establishing and/or maintaining DIP-mediated persistent infection.
Copyright © 2011 Elsevier Inc. All rights reserved.
Publication Date: 2011-02-15 PubMed ID: 21324502PubMed Central: PMC3060994DOI: 10.1016/j.virol.2011.01.025Google Scholar: Lookup
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Summary
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This research investigates the role of the UL4 protein in equine herpesvirus 1 (EHV-1), finding it unnecessary for the virus’s replication or pathogenesis and having an inhibitory effect on gene expression.
The Role and Impact of the UL4 Protein
- Often found in defective interfering particles (DIPs) of equine herpesvirus 1 (EHV-1), the UL4 protein, also known as UL4P, had an unknown function prior to this research.
- This research reveals that UL4P acts as an early gene that is activated purely by the immediate early protein. It is detected four hours after infection and is located throughout the cellular nucleus and cytoplasm.
- The UL4 protein was not seen in purified virions, suggesting that it is not incorporated into viral particles.
UL4 Protein and Virus Replication and Pathogenesis
- The research demonstrates that even in the absence of UL4P expression, EHV-1 remains infectious. This indicates that UL4P is not an essential part of the virus’s replication process.
- Even without UL4P, the virus displayed similar levels of cell tropism and pathogenic properties when examined in a mouse model, as compared to parental and revertant viruses.
Inhibitory Function of the UL4 Protein
- The research finds that the UL4P broadly inhibits gene expression, demonstrating its operating role and effects on the virus.
- This inhibitory function of the UL4 protein could point to a potential role it plays in establishing and/or maintaining DIP-mediated persistent infection.
- However, the exact method and extent of this inhibitory role, especially in regard to its potential for aiding persistent infection, needs further investigation.
Cite This Article
APA
Charvat RA, Breitenbach JE, Ahn B, Zhang Y, O'Callaghan DJ.
(2011).
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, 412(2), 366-377.
https://doi.org/10.1016/j.virol.2011.01.025 Publication
Researcher Affiliations
- Center for Molecular and Tumor Virology, Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130-3932, USA.
MeSH Terms
- Animals
- Cell Line
- Cell Nucleus / chemistry
- Chlorocebus aethiops
- Cytoplasm / chemistry
- Gene Expression Regulation
- Herpesvirus 1, Equid / pathogenicity
- Herpesvirus 1, Equid / physiology
- Host-Pathogen Interactions
- Humans
- Mice
- Promoter Regions, Genetic
- Rabbits
- Viral Proteins / metabolism
- Virus Replication
Grant Funding
- R01 AI022001 / NIAID NIH HHS
- P20 RR018724-08 / NCRR NIH HHS
- P20 RR018724 / NCRR NIH HHS
- R01 AI022001-22 / NIAID NIH HHS
- AI-22001 / NIAID NIH HHS
- P20-RR018724 / NCRR NIH HHS
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Citations
This article has been cited 6 times.- 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.
- Charvat RA, Zhang Y, O'Callaghan DJ. Deletion of the UL4 gene sequence of equine herpesvirus 1 precludes the generation of defective interfering particles.. Virus Genes 2012 Oct;45(2):295-303.
- 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.
- Ahn BC, Kim S, Zhang Y, Charvat RA, O'Callaghan DJ. The early UL3 gene of equine herpesvirus-1 encodes a tegument protein not essential for replication or virulence in the mouse.. Virology 2011 Nov 10;420(1):20-31.
- 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.
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