title: 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.
authors.affiliation: Department of Molecular Pathobiology, Hokkaido University Research Center for Zoonosis Control, Sapporo 001-0020, Japan.
authors.forename: Michihito
authors.initials: M
authors.lastname: Sasaki
authors.forename: Rie
authors.initials: R
authors.lastname: Hasebe
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Makino
authors.forename: Tadaki
authors.initials: T
authors.lastname: Suzuki
authors.forename: Hideto
authors.initials: H
authors.lastname: Fukushi
authors.forename: Minoru
authors.initials: M
authors.lastname: Okamoto
authors.forename: Kazuya
authors.initials: K
authors.lastname: Matsuda
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Taniyama
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Sawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Kimura
mesh_terms: D000818:Animals; D042783:Endothelial Cells / Q000821:virology; D005805:Genes, MHC Class I / Q000235:genetics* / Q000502:physiology; D005820:Genetic Testing; D006566:Herpesviridae Infections / Q000235:genetics / Q000276:immunology / Q000662:veterinary*; D004861:Herpesvirus 1, Equid / Q000472:pathogenicity*; D006734:Horse Diseases / Q000235:genetics / Q000276:immunology*; D006736:Horses / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells / Q000821:virology; D014759:Viral Envelope Proteins / Q000276:immunology*
chemical_list: D014759:Viral Envelope Proteins; C488988:glycoprotein D, Equid herpesvirus 1