title: Bovine herpesvirus 1 UL49.5 protein inhibits the transporter associated with antigen processing despite complex formation with glycoprotein M.
abstract: Bovine herpesvirus 1 (BHV-1) interferes with peptide translocation by the transporter associated with antigen processing (TAP). Recently, the UL49.5 gene product of BHV-1 was identified as the protein responsible for the observed inhibition of TAP. In BHV-1-infected cells and virions, the UL49.5 protein forms a complex with glycoprotein M (gM). Hence, it was investigated whether UL49.5 can combine the interactions with gM and the TAP complex. In cell lines constitutively expressing both UL49.5 and gM, UL49.5 appears to be required for functional processing of gM. Immunofluorescence-confocal laser scanning microscopy demonstrated that both proteins are interdependent for their redistribution from the endoplasmic reticulum to the trans-Golgi network. Remarkably, expression of cloned gM results in the abrogation of the UL49.5-mediated inhibition of TAP and prevents the degradation of the transporter. However, in BHV-1-infected cells, differences in UL49.5 and gM expression kinetics were seen to create a window of opportunity at the early stages of infection, during which time the UL49.5 protein can act on TAP without gM interference. Moreover, in later periods, non-gM-associated UL49.5 can be detected in addition to the UL49.5/gM complex. Thus, it has been deduced that different functions of UL49.5, editing of gM processing and inhibition of TAP, can be combined during BHV-1 infection.
authors.affiliation: Department of Medical Microbiology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands.
authors.forename: Andrea D
authors.initials: AD
authors.lastname: Lipińska
authors.forename: Danijela
authors.initials: D
authors.lastname: Koppers-Lalic
authors.forename: Michał
authors.initials: M
authors.lastname: Rychłowski
authors.forename: Pieter
authors.initials: P
authors.lastname: Admiraal
authors.forename: Frans A M
authors.initials: FA
authors.lastname: Rijsewijk
authors.forename: Krystyna
authors.initials: K
authors.lastname: Bieńkowska-Szewczyk
authors.forename: Emmanuel J H J
authors.initials: EJ
authors.lastname: Wiertz
mesh_terms: D018528:ATP-Binding Cassette Transporters; D000818:Animals; D002417:Cattle; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006566:Herpesviridae Infections; D007242:Herpesvirus 1, Bovine; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D046912:Multiprotein Complexes / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D014759:Viral Envelope Proteins / Q000502:physiology*; D014764:Viral Proteins / Q000378:metabolism*; D021601:trans-Golgi Network / Q000378:metabolism
chemical_list: D018528:ATP-Binding Cassette Transporters; D015395:Histocompatibility Antigens Class I; D046912:Multiprotein Complexes; C099455:UL49.5 protein, bovine herpesvirus type 1; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C046998:bovine herpesvirus type-1 glycoproteins; C477327:transporter associated with antigen processing (TAP)