Equid herpesvirus type 4 uses a restricted set of equine major histocompatibility complex class I proteins as entry receptors

J Gen Virol. 2014 Jul;95(Pt 7):1554-1563. doi: 10.1099/vir.0.066407-0. Epub 2014 Apr 10.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • DNA Mutational Analysis
  • Herpesvirus 1, Equid / physiology
  • Herpesvirus 4, Equid / physiology*
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / metabolism*
  • Horses
  • Humans
  • Mice
  • Mutagenesis, Site-Directed
  • Receptors, Virus / metabolism*
  • Virus Attachment
  • Virus Internalization*

Substances

  • Histocompatibility Antigens Class I
  • Receptors, Virus