Equid herpesvirus type 4 uses a restricted set of equine major histocompatibility complex class I proteins as entry receptors.
Equid herpesvirus type 1 (EHV-1) was shown to use an unusual receptor for cellular entry - MHC-I molecules. Here, we demonstrated that the closely related EHV, EHV-4, also uses this strategy for cellular invasion, both in equine cells in culture and in the heterologous, non-permissive murine mastocytoma cell line (P815) after stable transfection with horse MHC-I genes. Using a panel of P815 cell lines transfected with individual horse MHC-I genes, we provided support for the hypothesis that EHV-1 and EHV-4 target classical polymorphic MHC-I molecules as viral entry receptors. All known equine MHC-I molecules from the two principal classical polymorphic loci specify alanine at position 173 (A173), whilst other MHC-I loci encoded different amino acids at this position and did not permit viral entry. Site-directed mutagenesis of position 173 diminished or enhanced viral entry, depending upon the initial amino acid. However, there were other, as yet undefined, constraints to this process: MHC-I genes from two non-classical loci carried A173 but did not enable viral entry in P815 transfectants. Our study suggested that the capacity to bind MHC-I molecules arose in the common ancestor of EHV-1 and EHV-4. The widespread occurrence of A173 in classical polymorphic horse MHC-I molecules indicated that horses of most MHC haplotypes should be susceptible to infection via this entry portal.
Department of Virology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt.|Institut für Virologie, Robert von Ostertag-Haus, Zentrum für Infektionsmedizin, Freie Universität Berlin, 14163 Berlin, Germany.
Walid
W
Azab
Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Rebecca
R
Harman
Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Donald
D
Miller
Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Rebecca
R
Tallmadge
Department of Biology and Marine Biology, University of North Carolina Wilmington, Wilmington, NC 28403, USA.
Arthur R
AR
Frampton
Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Douglas F
DF
Antczak
Institut für Virologie, Robert von Ostertag-Haus, Zentrum für Infektionsmedizin, Freie Universität Berlin, 14163 Berlin, Germany.
Nikolaus
N
Osterrieder
D000818:Animals; D002460:Cell Line; D004252:DNA Mutational Analysis; D004861:Herpesvirus 1, Equid / Q000502:physiology; D023141:Herpesvirus 4, Equid / Q000502:physiology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D006736:Horses; D006801:Humans; D051379:Mice; D016297:Mutagenesis, Site-Directed; D011991:Receptors, Virus / Q000378:metabolism*; D053585:Virus Attachment; D053586:Virus Internalization
D015395:Histocompatibility Antigens Class I; D011991:Receptors, Virus