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
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- 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
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Citations
This article has been cited 3 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).
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- 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.
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