title: Identification and characterization of equine herpesvirus type 1 pUL56 and its role in virus-induced downregulation of major histocompatibility complex class I.
abstract: Major histocompatibility complex class I (MHC-I) molecules play an important role in host immunity to infection by presenting antigenic peptides to cytotoxic T lymphocytes (CTLs), which recognize and destroy virus-infected cells. Members of the Herpesviridae have developed multiple mechanisms to avoid CTL recognition by virtue of downregulation of MHC-I on the cell surface. We report here on an immunomodulatory protein involved in this process, pUL56, which is encoded by ORF1 of equine herpesvirus type 1 (EHV-1), an alphaherpesvirus. We show that EHV-1 pUL56 is a phosphorylated early protein which is expressed as different forms and predominantly localizes to Golgi membranes. In addition, the transmembrane (TM) domain of the type II membrane protein was shown to be indispensable for correct subcellular localization and a proper function. pUL56 by itself is not functional with respect to interference with MHC-I and likely needs another unidentified viral protein(s) to perform this action. Surprisingly, pUL49.5, an inhibitor of the transporter associated with antigen processing (TAP) and encoded by EHV-1 and related viruses, appeared not to be required for pUL56-induced early MHC-I downmodulation in infected cells. In conclusion, our data identify a new immunomodulatory protein, pUL56, involved in MHC-I downregulation which is unable to perform its function outside the context of viral infection.
authors.affiliation: Institut für Virologie, Freie Universität Berlin, Berlin, Germany. no.34@fu-berlin.de
authors.forename: Guanggang
authors.initials: G
authors.lastname: Ma
authors.forename: Silke
authors.initials: S
authors.lastname: Feineis
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Osterrieder
authors.forename: Gerlinde R
authors.initials: GR
authors.lastname: Van de Walle
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D015536:Down-Regulation; D015967:Gene Expression Regulation, Viral; D006566:Herpesviridae Infections / Q000235:genetics / Q000276:immunology / Q000662:veterinary*; D004861:Herpesvirus 1, Equid / Q000235:genetics / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology; D006734:Horse Diseases / Q000235:genetics* / Q000276:immunology; D006736:Horses; D006801:Humans; D008969:Molecular Sequence Data; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D015395:Histocompatibility Antigens Class I; D014764:Viral Proteins