@article{mbs:/content/journal/jgv/10.1099/vir.0.066407-0, author = "Azab, Walid and Harman, Rebecca and Miller, Donald and Tallmadge, Rebecca and Frampton, Arthur R. and Antczak, Douglas F. and Osterrieder, Nikolaus", title = "Equid herpesvirus type 4 uses a restricted set of equine major histocompatibility complex class I proteins as entry receptors", journal= "Journal of General Virology", year = "2014", volume = "95", number = "7", pages = "1554-1563", doi = "https://doi.org/10.1099/vir.0.066407-0", url = "https://www.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.066407-0", publisher = "Microbiology Society", issn = "1465-2099", type = "Journal Article", abstract = "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.", }