Modulation of transporter associated with antigen processing (TAP)-mediated peptide import into the endoplasmic reticulum by flavivirus infection.
In contrast to many other viruses that escape the cellular immune response by downregulating major histocompatibility complex (MHC) class I molecules, flavivirus infection can upregulate their cell surface expression. Previously we have presented evidence that during flavivirus infection, peptide supply to the endoplasmic reticulum is increased (A. Müllbacher and M. Lobigs, Immunity 3:207-214, 1995). Here we show that during the early phase of infection with different flaviviruses, the transport activity of the peptide transporter associated with antigen processing (TAP) is augmented by up to 50%. TAP expression is unaltered during infection, and viral but not host macromolecular synthesis is required for enhanced peptide transport. This study is the first demonstration of transient enhancement of TAP-dependent peptide import into the lumen of the endoplasmic reticulum as a consequence of a viral infection. We suggest that the increased supply of peptides for assembly with MHC class I molecules in flavivirus-infected cells accounts for the upregulation of MHC class I cell surface expression with the biological consequence of viral evasion of natural killer cell recognition.
Momburg
F
F
Department of Molecular Immunology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
Müllbacher
A
A
Lobigs
M
M
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D017951:Antigen Presentation; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005416:Flavivirus / Q000472:pathogenicity; D018177:Flavivirus Infections / Q000276:immunology / Q000503:physiopathology* / Q000821:virology; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D010455:Peptides / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D014779:Virus Replication
D018528:ATP-Binding Cassette Transporters; D015395:Histocompatibility Antigens Class I; D010455:Peptides