• Open Access

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

Authors

  • Michihito Sasaki,

    1. Department of Molecular Pathobiology, Hokkaido University Research Center for Zoonosis Control, Sapporo 001-0020, Japan
    2. Global COE Program, Hokkaido University, Sapporo 060-0818, Japan
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  • Rie Hasebe,

    1. Department of Molecular Pathobiology, Hokkaido University Research Center for Zoonosis Control, Sapporo 001-0020, Japan
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    • Present address: Laboratory of Veterinary Hygiene, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.

  • Yoshinori Makino,

    1. Department of Molecular Pathobiology, Hokkaido University Research Center for Zoonosis Control, Sapporo 001-0020, Japan
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    • Present address: Career-Path Promotion Unit for Young Life Scientists/ICDO, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.

  • Tadaki Suzuki,

    1. Department of Molecular Pathobiology, Hokkaido University Research Center for Zoonosis Control, Sapporo 001-0020, Japan
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    • Present address: Department of Pathology, National Institute of Infectious Diseases, Musashimurayama, Tokyo 208-0011, Japan.

  • Hideto Fukushi,

    1. Department of Applied Veterinary Sciences, United Graduate School of Veterinary Sciences, Gifu University, Gifu 501-1193, Japan
    2. Laboratory of Veterinary Microbiology, Faculty of Applied Biological Sciences, Gifu University, Gifu 501-1193, Japan
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  • Minoru Okamoto,

    1. Department of Veterinary Pathology, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido 069-8501, Japan
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  • Kazuya Matsuda,

    1. Department of Veterinary Pathology, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido 069-8501, Japan
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  • Hiroyuki Taniyama,

    1. Department of Veterinary Pathology, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido 069-8501, Japan
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  • Hirofumi Sawa,

    1. Department of Molecular Pathobiology, Hokkaido University Research Center for Zoonosis Control, Sapporo 001-0020, Japan
    2. Global COE Program, Hokkaido University, Sapporo 060-0818, Japan
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  • Takashi Kimura

    Corresponding author
    1. Department of Molecular Pathobiology, Hokkaido University Research Center for Zoonosis Control, Sapporo 001-0020, Japan
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kimura@czc.hokudai.ac.jp

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.

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