Peptide transport activity of the transporter associated with antigen processing (TAP) is inhibited by an early protein of equine herpesvirus-1.
Abstract: Equine herpesvirus-1 (EHV-1) downregulates surface expression of major histocompatibility complex (MHC) class I molecules on infected cells. The objective of this study was to investigate whether EHV-1 interferes with peptide translocation by the transporter associated with antigen processing (TAP) and to identify the proteins responsible. Using an in vitro transport assay, we showed that EHV-1 inhibited transport of peptides by TAP as early as 2 h post-infection (p.i). Complete shutdown of peptide transport was observed by 8 h p.i. Furthermore, pulse-chase experiments revealed that maturation of class I molecules in the endoplasmic reticulum (ER) was delayed in EHV-1-infected cells, which may be due to reduced availability of peptides in the ER as a result of TAP inhibition. Metabolic inhibition studies indicated that an early protein(s) of EHV-1 is responsible for this effect.
Publication Date: 2004-02-11 PubMed ID: 14769892DOI: 10.1099/vir.0.19563-0Google Scholar: Lookup
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- Comparative Study
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research investigates how Equine herpesvirus-1 (EHV-1), a virus affecting horses, weakens the defensive response of infected cells by inhibiting a protein responsible for antigen processing.
Research Objective
- The research was conducted with an aim to understand if and how EHV-1 interrupts the peptide (a type of molecule) translocation by the transporter associated with antigen processing (TAP), a type of protein involved in immune responses. The study also sought to identify which EHV-1 proteins are responsible for this interference.
Methodology and Findings
- The researchers used an in vitro (outside of a living organism) transport assay. They observed that EHV-1 started inhibiting the transport of peptides via TAP as soon as 2 hours after infection, with a complete shutdown of peptide transport occurring around 8 hours post-infection.
- Through further experiments, it was uncovered that the maturation of class I molecules within the endoplasmic reticulum (ER)— a type of organelle within cells —was delayed in EHV-1 infected cells. This might be due to reduced peptide availability in the ER resulting from TAP inhibition.
- Following metabolic inhibition studies, it was indicated an early protein(s) associated with the EHV-1 is responsible for this disruptive effect. Thus, the virus uses these early proteins to interfere with an early stage of the cell’s immune response and prevent it from fighting the infection effectively.
Conclusion
- This research contributes to the understanding of how the Equine herpesvirus-1 (EHV-1) manages to downregulate the surface expression of major histocompatibility complex (MHC) class I molecules (an important part of immune response) on infected cells, making them more susceptible to the disease.
Cite This Article
APA
Ambagala APN, Gopinath RS, Srikumaran S.
(2004).
Peptide transport activity of the transporter associated with antigen processing (TAP) is inhibited by an early protein of equine herpesvirus-1.
J Gen Virol, 85(Pt 2), 349-353.
https://doi.org/10.1099/vir.0.19563-0 Publication
Researcher Affiliations
- Department of Veterinary and Biomedical Sciences, University of Nebraska-Lincoln, NE 68583-0905, USA.
- Department of Veterinary and Biomedical Sciences, University of Nebraska-Lincoln, NE 68583-0905, USA.
- Department of Veterinary and Biomedical Sciences, University of Nebraska-Lincoln, NE 68583-0905, USA.
MeSH Terms
- ATP-Binding Cassette Transporters
- Animals
- Biological Transport, Active
- Cell Line
- Down-Regulation
- Endoplasmic Reticulum / metabolism
- Herpesvirus 1, Equid / immunology
- Herpesvirus 1, Equid / metabolism
- Histocompatibility Antigens Class I / metabolism
- Immediate-Early Proteins / metabolism
- Membrane Transport Modulators
- Membrane Transport Proteins / antagonists & inhibitors
- Membrane Transport Proteins / metabolism
Citations
This article has been cited 15 times.- Zarski LM, Vaala WE, Barnett DC, Bain FT, Soboll Hussey G. A Live-Attenuated Equine Influenza Vaccine Stimulates Innate Immunity in Equine Respiratory Epithelial Cell Cultures That Could Provide Protection From Equine Herpesvirus 1.. Front Vet Sci 2021;8:674850.
- Jones C. Bovine Herpesvirus 1 Counteracts Immune Responses and Immune-Surveillance to Enhance Pathogenesis and Virus Transmission.. Front Immunol 2019;10:1008.
- Washburne AD, Crowley DE, Becker DJ, Olival KJ, Taylor M, Munster VJ, Plowright RK. Taxonomic patterns in the zoonotic potential of mammalian viruses.. PeerJ 2018;6:e5979.
- Poelaert KCK, Van Cleemput J, Laval K, Favoreel HW, Soboll Hussey G, Maes RK, Nauwynck HJ. Abortigenic but Not Neurotropic Equine Herpes Virus 1 Modulates the Interferon Antiviral Defense.. Front Cell Infect Microbiol 2018;8:312.
- Bergmann T, Moore C, Sidney J, Miller D, Tallmadge R, Harman RM, Oseroff C, Wriston A, Shabanowitz J, Hunt DF, Osterrieder N, Peters B, Antczak DF, Sette A. The common equine class I molecule Eqca-1*00101 (ELA-A3.1) is characterized by narrow peptide binding and T cell epitope repertoires.. Immunogenetics 2015 Nov;67(11-12):675-89.
- Vasireddi M, Hilliard J. Herpes B virus, macacine herpesvirus 1, breaks simplex virus tradition via major histocompatibility complex class I expression in cells from human and macaque hosts.. J Virol 2012 Dec;86(23):12503-11.
- Said A, Azab W, Damiani A, Osterrieder N. Equine herpesvirus type 4 UL56 and UL49.5 proteins downregulate cell surface major histocompatibility complex class I expression independently of each other.. J Virol 2012 Aug;86(15):8059-71.
- Ma G, Feineis S, Osterrieder N, Van de Walle GR. Identification and characterization of equine herpesvirus type 1 pUL56 and its role in virus-induced downregulation of major histocompatibility complex class I.. J Virol 2012 Apr;86(7):3554-63.
- Jones C. Regulation of Innate Immune Responses by Bovine Herpesvirus 1 and Infected Cell Protein 0 (bICP0).. Viruses 2009 Sep;1(2):255-75.
- Soboll Hussey G, Hussey SB, Wagner B, Horohov DW, Van de Walle GR, Osterrieder N, Goehring LS, Rao S, Lunn DP. Evaluation of immune responses following infection of ponies with an EHV-1 ORF1/2 deletion mutant.. Vet Res 2011 Feb 7;42(1):23.
- Kurtz BM, Singletary LB, Kelly SD, Frampton AR Jr. Equus caballus major histocompatibility complex class I is an entry receptor for equine herpesvirus type 1.. J Virol 2010 Sep;84(18):9027-34.
- Koppers-Lalic D, Verweij MC, Lipińska AD, Wang Y, Quinten E, Reits EA, Koch J, Loch S, Marcondes Rezende M, Daus F, Bieńkowska-Szewczyk K, Osterrieder N, Mettenleiter TC, Heemskerk MH, Tampé R, Neefjes JJ, Chowdhury SI, Ressing ME, Rijsewijk FA, Wiertz EJ. Varicellovirus UL 49.5 proteins differentially affect the function of the transporter associated with antigen processing, TAP.. PLoS Pathog 2008 May 30;4(5):e1000080.
- Schölz C, Tampé R. The intracellular antigen transport machinery TAP in adaptive immunity and virus escape mechanisms.. J Bioenerg Biomembr 2005 Dec;37(6):509-15.
- Loch S, Tampé R. Viral evasion of the MHC class I antigen-processing machinery.. Pflugers Arch 2005 Dec;451(3):409-17.
- Koppers-Lalic D, Reits EA, Ressing ME, Lipinska AD, Abele R, Koch J, Marcondes Rezende M, Admiraal P, van Leeuwen D, Bienkowska-Szewczyk K, Mettenleiter TC, Rijsewijk FA, Tampé R, Neefjes J, Wiertz EJ. Varicelloviruses avoid T cell recognition by UL49.5-mediated inactivation of the transporter associated with antigen processing.. Proc Natl Acad Sci U S A 2005 Apr 5;102(14):5144-9.
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