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Bovine herpesvirus 1 interferes with TAP-dependent peptide transport and intracellular trafficking of MHC class I molecules in human cells.

Abstract
Bovine herpesvirus 1 (BoHV-1), the cause of infectious bovine rhinotracheitis and infectious pustular vulvovaginitis in cattle, establishes a lifelong infection, despite the presence of antiviral immunity in the host. BoHV-1 has been shown to elude the host immune system, but the viral gene products responsible for this interference have not yet been identified. Studies aiming at the identification of BoHV-1-encoded immune evasion genes have been hampered by the lack of bovine-specific immunological reagents. Some of the immune evasion molecules identified for other herpesviruses are host species specific; others can act across the species barrier. In this study, experiments were performed to investigate whether BoHV-1 can infect human cells and interfere with antigen processing and presentation in these cells. A human melanoma cell line, Mel JuSo, appeared to be permissive for BoHV-1 infection. BoHV-1 induced expression of major viral glycoproteins at the surface of these cells and produced progeny virus up to 10(5) plaque forming units per ml. BoHV-1 infection resulted in impaired intracellular transport of human MHC class I molecules and inhibition of human TAP. These data indicate that the BoHV-1-encoded molecule(s) that block antigen presentation in bovine cells are able to interact with homologous components of the human MHC class I presentation pathway. The fact that immune evasion by BoHV-1 can be studied in human cells will facilitate the identification of the BoHV-1 gene products involved in this process. Moreover, the data presented here suggest that the BoHV-1 encoded inhibitors of antigen presentation represent potential immune suppressive agents for use in humans.
AuthorsD Koppers-Lalic, M Rychlowski, D van Leeuwen, F A M Rijsewijk, M E Ressing, J J Neefjes, K Bienkowska-Szewczyk, E J H J Wiertz
JournalArchives of virology (Arch Virol) Vol. 148 Issue 10 Pg. 2023-37 (Oct 2003) ISSN: 0304-8608 [Print] Austria
PMID14551822 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • ATP-Binding Cassette Transporters
  • Histocompatibility Antigens Class I
  • Peptides
Topics
  • ATP-Binding Cassette Transporters (metabolism)
  • Animals
  • Cattle
  • Cell Line
  • Herpesvirus 1, Bovine (pathogenicity)
  • Histocompatibility Antigens Class I (metabolism)
  • Humans
  • Peptides (metabolism)
  • Protein Transport
  • Tumor Cells, Cultured
  • Virus Replication

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