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Genes to cells : devoted to molecular & cellular mechanisms2011; 16(4); 343-357; doi: 10.1111/j.1365-2443.2011.01491.x

Equine major histocompatibility complex class I molecules act as entry receptors that bind to equine herpesvirus-1 glycoprotein D.

Abstract: The endotheliotropism of equine herpesvirus-1 (EHV-1) leads to encephalomyelitis secondary to vasculitis and thrombosis in the infected horse central nervous system (CNS). To identify the host factors involved in EHV-1 infection of CNS endothelial cells, we performed functional cloning using an equine brain microvascular endothelial cell cDNA library. Exogenous expression of equine major histocompatibility complex (MHC) class I heavy chain genes conferred susceptibility to EHV-1 infection in mouse NIH3T3 cells, which are not naturally susceptible to EHV-1 infection. Equine MHC class I molecules bound to EHV-1 glycoprotein D (gD), and both anti-gD antibodies and a soluble form of gD blocked viral entry into NIH3T3 cells stably expressing the equine MHC class I heavy chain gene (3T3-A68 cells). Treatment with an anti-equine MHC class I monoclonal antibody blocked EHV-1 entry into 3T3-A68 cells, equine dermis (E. Derm) cells and equine brain microvascular endothelial cells. In addition, inhibition of cell surface expression of MHC class I molecules in E. Derm cells drastically reduced their susceptibility to EHV-1 infection. These results suggest that equine MHC class I is a functional gD receptor that plays a pivotal role in EHV-1 entry into equine cells.
Publication Date: 2011-02-10 PubMed ID: 21306483PubMed Central: PMC3118799DOI: 10.1111/j.1365-2443.2011.01491.xGoogle Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

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 article discusses how equine major histocompatibility complex (MHC) class I molecules are functional receptors for equine herpesvirus-1 (EHV-1) in horses, crucial to the virus’s ability to infect equine cells.

Research Objective and Methods

  • The research primarily aims to understand the factors involved in EHV-1 infection of the central nervous system (CNS) in horses. This is critical as the virus causes encephalomyelitis in horses due to vasculitis and thrombosis of the infected CNS.
  • Functional cloning was used in this study, using a cDNA library derived from equine brain microvascular endothelial cells.
  • The researchers also studied the susceptibility of mouse NIH3T3 cells to EHV-1 infection after expressing equine MHC class I heavy chain genes.

Findings of the Study

  • Equine MHC class I molecules were found to bind to EHV-1 glycoprotein D (gD), and this connection was found to be potentially disrupted by using either an anti-gD antibody or a soluble form of the gD protein.
  • Notably, the research discovered that when mouse cells were altered to express the equine MHC Class I genes, they became susceptible to EHV-1, proving that MHC Class I molecules serve as an entry point for the virus.
  • The observed susceptibility was not naturally present in the mouse cells, indicating the crucial role of the horse specific MHC class I molecules in the infection process.

Implications and Conclusions

  • This research has important implications for understanding the pathways of EHV-1 infection in horses and potentially for the treatment and prevention of such infections.
  • Inhibiting cell surface expression of MHC class I molecules reduced the cells’ susceptibility to EHV-1 infection significantly.
  • These findings allude to strategies to prevent or reduce EHV-1 infection, such as therapeutics blocking the interaction between the virus’s gD protein and the MHC Class I molecules on equine cells.

Cite This Article

APA
Sasaki M, Hasebe R, Makino Y, Suzuki T, Fukushi H, Okamoto M, Matsuda K, Taniyama H, Sawa H, Kimura T. (2011). Equine major histocompatibility complex class I molecules act as entry receptors that bind to equine herpesvirus-1 glycoprotein D. Genes Cells, 16(4), 343-357. https://doi.org/10.1111/j.1365-2443.2011.01491.x

Publication

ISSN: 1365-2443
NlmUniqueID: 9607379
Country: England
Language: English
Volume: 16
Issue: 4
Pages: 343-357

Researcher Affiliations

Sasaki, Michihito
  • Department of Molecular Pathobiology, Hokkaido University Research Center for Zoonosis Control, Sapporo 001-0020, Japan.
Hasebe, Rie
    Makino, Yoshinori
      Suzuki, Tadaki
        Fukushi, Hideto
          Okamoto, Minoru
            Matsuda, Kazuya
              Taniyama, Hiroyuki
                Sawa, Hirofumi
                  Kimura, Takashi

                    MeSH Terms

                    • Animals
                    • Endothelial Cells / virology
                    • Genes, MHC Class I / genetics
                    • Genes, MHC Class I / physiology
                    • Genetic Testing
                    • Herpesviridae Infections / genetics
                    • Herpesviridae Infections / immunology
                    • Herpesviridae Infections / veterinary
                    • Herpesvirus 1, Equid / pathogenicity
                    • Horse Diseases / genetics
                    • Horse Diseases / immunology
                    • Horses / immunology
                    • Mice
                    • Molecular Sequence Data
                    • NIH 3T3 Cells / virology
                    • Viral Envelope Proteins / immunology

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                    Citations

                    This article has been cited 15 times.
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