title: The capacity of UL49.5 proteins to inhibit TAP is widely distributed among members of the genus Varicellovirus.
abstract: The lifelong infection by varicelloviruses is characterized by a fine balance between the host immune response and immune evasion strategies used by these viruses. Virus-derived peptides are presented to cytotoxic T lymphocytes by major histocompatibility complex (MHC) class I molecules. The transporter associated with antigen processing (TAP) transports the peptides from the cytosol into the endoplasmic reticulum, where the loading of MHC-I molecules occurs. The varicelloviruses bovine herpesvirus 1 (BoHV-1), pseudorabies virus, and equid herpesviruses 1 and 4 have been found to encode a UL49.5 protein that inhibits TAP-mediated peptide transport. To investigate to what extent UL49.5-mediated TAP inhibition is conserved within the family of Alphaherpesvirinae, the homologs of another five varicelloviruses, one mardivirus, and one iltovirus were studied. The UL49.5 proteins of BoHV-5, bubaline herpesvirus 1, cervid herpesvirus 1, and felid herpesvirus 1 were identified as potent TAP inhibitors. The varicella-zoster virus and simian varicellovirus UL49.5 proteins fail to block TAP; this is not due to the absence of viral cofactors that might assist in this process, since cells infected with these viruses did not show reduced TAP function either. The UL49.5 homologs of the mardivirus Marek's disease virus 1 and the iltovirus infectious laryngotracheitis virus did not block TAP, suggesting that the capacity to inhibit TAP via UL49.5 has been acquired by varicelloviruses only. A phylogenetic analysis of viruses that inhibit TAP through their UL49.5 proteins reveals an interesting hereditary pattern, pointing toward the presence of this capacity in defined clades within the genus Varicellovirus.
authors.affiliation: Department of Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, Netherlands.
authors.forename: Marieke C
authors.initials: MC
authors.lastname: Verweij
authors.forename: Andrea D
authors.initials: AD
authors.lastname: Lipinska
authors.forename: Danijela
authors.initials: D
authors.lastname: Koppers-Lalic
authors.forename: Wouter F
authors.initials: WF
authors.lastname: van Leeuwen
authors.forename: Jeffrey I
authors.initials: JI
authors.lastname: Cohen
authors.forename: Paul R
authors.initials: PR
authors.lastname: Kinchington
authors.forename: Ilhem
authors.initials: I
authors.lastname: Messaoudi
authors.forename: Krystyna
authors.initials: K
authors.lastname: Bienkowska-Szewczyk
authors.forename: Maaike E
authors.initials: ME
authors.lastname: Ressing
authors.forename: Frans A M
authors.initials: FA
authors.lastname: Rijsewijk
authors.forename: Emmanuel J H J
authors.initials: EJ
authors.lastname: Wiertz
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D002418:Cattle Diseases / Q000276:immunology / Q000821:virology; D002460:Cell Line; D015536:Down-Regulation; D006566:Herpesviridae Infections / Q000276:immunology* / Q000662:veterinary* / Q000821:virology; D007242:Herpesvirus 1, Bovine / Q000145:classification / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D016415:Sequence Alignment; D018140:Varicellovirus / Q000145:classification / Q000235:genetics / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D018528:ATP-Binding Cassette Transporters; C099455:UL49.5 protein, bovine herpesvirus type 1; D014759:Viral Envelope Proteins; C477327:transporter associated with antigen processing (TAP)