Publikationsdatenbank

Equid herpesvirus type 4 uses a restricted set of equine major histocompatibility complex class I proteins as entry receptors (2014)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Azab, Walid (WE 5)

Harman, Rebecca

Miller, Donald

Tallmadge, Rebecca

Frampton, Arthur R

Antczak, Douglas F

Osterrieder, Nikolaus (WE 5)

Quelle

The journal of general virology

Bandzählung: 95

Heftzählung: Pt 7

Seiten: 1554 – 1563

ISSN: 0022-1317

Sprache

Englisch

Verweise

DOI: 10.1099/vir.0.066407-0

Pubmed: 24722677

Kontakt

Institut für Virologie

Robert-von-Ostertag-Str. 7-13
14163 Berlin
+49 30 838 51833
virologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

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.