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Single amino acid residue in the A2 domain of major histocompatibility complex class I is involved in the efficiency of equine herpesvirus-1 entry.
Abstract: Equine herpesvirus-1 (EHV-1), an α-herpesvirus of the family Herpesviridae, causes respiratory disease, abortion, and encephalomyelitis in horses. EHV-1 utilizes equine MHC class I molecules as entry receptors. However, hamster MHC class I molecules on EHV-1-susceptible CHO-K1 cells play no role in EHV-1 entry. To identify the MHC class I molecule region that is responsible for EHV-1 entry, domain exchange and site-directed mutagenesis experiments were performed, in which parts of the extracellular region of hamster MHC class I (clone C5) were replaced with corresponding sequences from equine MHC class I (clone A68). Substitution of alanine for glutamine at position 173 (Q173A) within the α2 domain of the MHC class I molecule enabled hamster MHC class I C5 to mediate EHV-1 entry into cells. Conversely, substitution of glutamine for alanine at position 173 (A173Q) in equine MHC class I A68 resulted in loss of EHV-1 receptor function. Equine MHC class I clone 3.4, which possesses threonine at position 173, was unable to act as an EHV-1 receptor. Substitution of alanine for threonine at position 173 (T173A) enabled MHC class I 3.4 to mediate EHV-1 entry into cells. These results suggest that the amino acid residue at position 173 of the MHC class I molecule is involved in the efficiency of EHV-1 entry.
Publication Date: 2011-09-26 PubMed ID: 21949188PubMed Central: PMC3234761DOI: 10.1074/jbc.M111.251751Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- Non-U.S. Gov't
- Amino Acid Sequence
- Animal Science
- Diagnosis
- Disease
- Disease Diagnosis
- Disease Etiology
- Equine Diseases
- Equine Health
- Equine Herpesvirus
- Genetics
- Horses
- Immunology
- Infection
- Infectious Disease
- Major Histocompatibility Complex (MHC)
- Molecular biology
- Respiratory Disease
- Veterinary Medicine
- Veterinary Research
- Virology
- Virus
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
The research study explored the role of a particular amino acid in the A2 domain of the major histocompatibility complex class I in the entry efficiency of equine herpesvirus-1 (EHV-1). Through various experiments, it was found that the presence of alanine rather than glutamine or threonine at position 173 greatly increased the efficiency of EHV-1 entry into cells.
Research Context
- Equine herpesvirus-1 (EHV-1) is a virus from the alpha-herpesvirus family that is known to cause various diseases in horses including respiratory issues, abortions, and encephalomyelitis.
- This virus utilizes equine MHC (major histocompatibility complex) class I molecules as a doorway or entry receptor into its host cells. Interestingly, it should be noted that the study highlighted that the MHC class I molecules in hamsters did not have the same facilitative effect on EHV-1 contagion.
Methodology of the Study
- To better understand the intricacies of EHV-1 entry, researchers conducted domain exchange and site-directed mutagenesis experiments. These involved replacing specific segments of the hamster MHC class I molecule with corresponding sections from the equine MHC class I molecule.
- This approach allowed researchers to identify the specific region of the MHC class I molecule that plays a critical role in enabling EHV-1 entry.
Key Findings
- Through these experiments, researchers discovered that replacing glutamine with alanine at position 173 within the α2 domain of the MHC class I molecule resulted in increased efficacy of EHV-1 entry into cells — A move titled “Q173A”.
- If the process was reversed, replacing alanine with glutamine at position 173 in the equine MHC class I – known as “A173Q” – then the EHV-1 receptor function was lost.
- Additionally, an equine MHC class I that naturally possesses threonine at position 173 was found to be ineffective as an EHV-1 receptor. However, when threonine was substituted with alanine – “T173A” – the resulting MHC molecule was able to successfully facilitate EHV-1 entry into cells.
Conclusion of the Research
- The research concluded that the amino acid residue present at position 173 of the MHC class I molecule considerably impacts the efficiency with which EHV-1 can infect cells.
- This finding potentially points to new avenues for inhibition and treatment of diseases caused by EHV-1 virus in horses.
Cite This Article
APA
Sasaki M, Kim E, Igarashi M, Ito K, Hasebe R, Fukushi H, Sawa H, Kimura T.
(2011).
Single amino acid residue in the A2 domain of major histocompatibility complex class I is involved in the efficiency of equine herpesvirus-1 entry.
J Biol Chem, 286(45), 39370-39378.
https://doi.org/10.1074/jbc.M111.251751 Publication
Researcher Affiliations
- Department of Molecular Pathobiology, Research Center for Zoonosis Control, Hokkaido University, Sapporo 001-0020, Japan.
MeSH Terms
- Amino Acid Substitution
- Animals
- CHO Cells
- Cricetinae
- Cricetulus
- Herpesvirus 1, Equid / genetics
- Herpesvirus 1, Equid / immunology
- Herpesvirus 1, Equid / metabolism
- Histocompatibility Antigens Class I / genetics
- Histocompatibility Antigens Class I / immunology
- Histocompatibility Antigens Class I / metabolism
- Horses
- Humans
- Mice
- Mutagenesis, Site-Directed
- Mutation, Missense
- NIH 3T3 Cells
- Rabbits
- Virus Internalization
References
This article includes 27 references
- Patel JR, Heldens J. Equine herpesviruses 1 (EHV-1) and 4 (EHV-4)--epidemiology, disease and immunoprophylaxis: a brief review.. Vet J 2005 Jul;170(1):14-23.
- Stierstorfer B, Eichhorn W, Schmahl W, Brandmüller C, Kaaden OR, Neubauer A. Equine herpesvirus type 1 (EHV-1) myeloencephalopathy: a case report.. J Vet Med B Infect Dis Vet Public Health 2002 Feb;49(1):37-41.
- Studdert MJ, Hartley CA, Dynon K, Sandy JR, Slocombe RF, Charles JA, Milne ME, Clarke AF, El-Hage C. Outbreak of equine herpesvirus type 1 myeloencephalitis: new insights from virus identification by PCR and the application of an EHV-1-specific antibody detection ELISA.. Vet Rec 2003 Oct 4;153(14):417-23.
- Kohn C. W., Reed S. M., Sofaly C. D., Henninger R. W., Saville W. J., Allen G. P., Premanadan C. (2006) Clin. Techniques Equine Practice 5, 60–66
- Osterrieder N. Construction and characterization of an equine herpesvirus 1 glycoprotein C negative mutant.. Virus Res 1999 Feb;59(2):165-77.
- Sugahara Y, Matsumura T, Kono Y, Honda E, Kida H, Okazaki K. Adaptation of equine herpesvirus 1 to unnatural host led to mutation of the gC resulting in increased susceptibility of the virus to heparin.. Arch Virol 1997;142(9):1849-56.
- Frampton AR Jr, Stolz DB, Uchida H, Goins WF, Cohen JB, Glorioso JC. Equine herpesvirus 1 enters cells by two different pathways, and infection requires the activation of the cellular kinase ROCK1.. J Virol 2007 Oct;81(20):10879-89.
- Hasebe R, Sasaki M, Sawa H, Wada R, Umemura T, Kimura T. Infectious entry of equine herpesvirus-1 into host cells through different endocytic pathways.. Virology 2009 Oct 25;393(2):198-209.
- Csellner H, Walker C, Wellington JE, McLure LE, Love DN, Whalley JM. EHV-1 glycoprotein D (EHV-1 gD) is required for virus entry and cell-cell fusion, and an EHV-1 gD deletion mutant induces a protective immune response in mice.. Arch Virol 2000;145(11):2371-85.
- Frampton AR Jr, Goins WF, Cohen JB, von Einem J, Osterrieder N, O'Callaghan DJ, Glorioso JC. Equine herpesvirus 1 utilizes a novel herpesvirus entry receptor.. J Virol 2005 Mar;79(5):3169-73.
- Whalley JM, Ruitenberg KM, Sullivan K, Seshadri L, Hansen K, Birch D, Gilkerson JR, Wellington JE. Host cell tropism of equine herpesviruses: glycoprotein D of EHV-1 enables EHV-4 to infect a non-permissive cell line.. Arch Virol 2007;152(4):717-25.
- Van de Walle GR, Peters ST, VanderVen BC, O'Callaghan DJ, Osterrieder N. Equine herpesvirus 1 entry via endocytosis is facilitated by alphaV integrins and an RSD motif in glycoprotein D.. J Virol 2008 Dec;82(23):11859-68.
- 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.
- Sasaki M, Hasebe R, Makino Y, Suzuki T, Fukushi H, Okamoto M, Matsuda K, Taniyama H, Sawa H, Kimura T. Equine major histocompatibility complex class I molecules act as entry receptors that bind to equine herpesvirus-1 glycoprotein D.. Genes Cells 2011 Apr;16(4):343-57.
- Janeway C. A., Travers P., Walport M., Shlomchik M. (2005) Immunobiology, 6th Ed., pp. 169–201, Garland Science Publishing, New York
- Tallmadge RL, Campbell JA, Miller DC, Antczak DF. Analysis of MHC class I genes across horse MHC haplotypes.. Immunogenetics 2010 Mar;62(3):159-72.
- Tallmadge RL, Lear TL, Antczak DF. Genomic characterization of MHC class I genes of the horse.. Immunogenetics 2005 Nov;57(10):763-74.
- Ibrahim el SM, Pagmajav O, Yamaguchi T, Matsumura T, Fukushi H. Growth and virulence alterations of equine herpesvirus 1 by insertion of a green fluorescent protein gene in the intergenic region between ORFs 62 and 63.. Microbiol Immunol 2004;48(11):831-42.
- Eswar N, John B, Mirkovic N, Fiser A, Ilyin VA, Pieper U, Stuart AC, Marti-Renom MA, Madhusudhan MS, Yerkovich B, Sali A. Tools for comparative protein structure modeling and analysis.. Nucleic Acids Res 2003 Jul 1;31(13):3375-80.
- Shen MY, Sali A. Statistical potential for assessment and prediction of protein structures.. Protein Sci 2006 Nov;15(11):2507-24.
- Still W. C., Tempczyk A., Hawley R. C., Hendrickson T. (1990) J. Am. Chem. Soc. 112, 6127–6129
- Tsui V, Case DA. Theory and applications of the generalized Born solvation model in macromolecular simulations.. Biopolymers 2000-2001;56(4):275-91.
- Laskowski R. A., MacArthur M. W., Moss D. S., Thornton J. M. (1993) J. Appl. Crystallog. 26, 283–291
- Eisenberg D, Lüthy R, Bowie JU. VERIFY3D: assessment of protein models with three-dimensional profiles.. Methods Enzymol 1997;277:396-404.
- DeLano WL. The PyMOL Molecular Graphics System. 2002 DeLano Scientific, San Carlos, CA.
- Furukawa H, Iizuka K, Poursine-Laurent J, Shastri N, Yokoyama WM. A ligand for the murine NK activation receptor Ly-49D: activation of tolerized NK cells from beta 2-microglobulin-deficient mice.. J Immunol 2002 Jul 1;169(1):126-36.
- Bjorkman PJ, Parham P. Structure, function, and diversity of class I major histocompatibility complex molecules.. Annu Rev Biochem 1990;59:253-88.
Citations
This article has been cited 4 times.- Vasoya D, Tzelos T, Benedictus L, Karagianni AE, Pirie S, Marr C, Oddsdóttir C, Fintl C, Connelley T. High-Resolution Genotyping of Expressed Equine MHC Reveals a Highly Complex MHC Structure. Genes (Basel) 2023 Jul 10;14(7).
- Kremling V, Loll B, Pach S, Dahmani I, Weise C, Wolber G, Chiantia S, Wahl MC, Osterrieder N, Azab W. Crystal structures of glycoprotein D of equine alphaherpesviruses reveal potential binding sites to the entry receptor MHC-I. Front Microbiol 2023;14:1197120.
- Courchesne MJ, White MC, Stanfield BA, Frampton AR Jr. Equine herpesvirus type 1-mediated oncolysis of human glioblastoma multiforme cells. J Virol 2012 Mar;86(5):2882-6.
- Eady NA, Holmes C, Schnabel C, Babasyan S, Wagner B. Equine herpesvirus type 1 (EHV-1) replication at the upper respiratory entry site is inhibited by neutralizing EHV-1-specific IgG1 and IgG4/7 mucosal antibodies. J Virol 2024 Jun 13;98(6):e0025024.
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