Bovine herpesvirus 1 interferes with TAP-dependent peptide transport and intracellular trafficking of MHC class I molecules in human cells.
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.
Koppers-Lalic
D
D
Department of Medical Microbiology, Center of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
Rychlowski
M
M
van Leeuwen
D
D
Rijsewijk
F A M
FA
Ressing
M E
ME
Neefjes
J J
JJ
Bienkowska-Szewczyk
K
K
Wiertz
E J H J
EJ
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D002460:Cell Line; D007242:Herpesvirus 1, Bovine / Q000472:pathogenicity*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D010455:Peptides / Q000378:metabolism*; D021381:Protein Transport; D014407:Tumor Cells, Cultured; D014779:Virus Replication
D018528:ATP-Binding Cassette Transporters; D015395:Histocompatibility Antigens Class I; D010455:Peptides