title: 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.
authors.affiliation: Department of Molecular Pathobiology, Research Center for Zoonosis Control, Hokkaido University, Sapporo 001-0020, Japan.
authors.forename: Michihito
authors.initials: M
authors.lastname: Sasaki
authors.forename: Eunmi
authors.initials: E
authors.lastname: Kim
authors.forename: Manabu
authors.initials: M
authors.lastname: Igarashi
authors.forename: Kimihito
authors.initials: K
authors.lastname: Ito
authors.forename: Rie
authors.initials: R
authors.lastname: Hasebe
authors.forename: Hideto
authors.initials: H
authors.lastname: Fukushi
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Sawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Kimura
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004861:Herpesvirus 1, Equid / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006736:Horses; D006801:Humans; D051379:Mice; D016297:Mutagenesis, Site-Directed; D020125:Mutation, Missense; D041681:NIH 3T3 Cells; D011817:Rabbits; D053586:Virus Internalization
chemical_list: D015395:Histocompatibility Antigens Class I