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. Previou sly we have presented evidence that during flavivirus infection, peptide su pply to the endoplasmic reticulum is increased (A. Mullbacher and M. Lobigs , Immunity 3:207-214, 1995). Here we show that during the early phase of in fection 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 m acromolecular synthesis is required for enhanced peptide transport. This st udy is the first demonstration of transient enhancement of TAP-dependent pe ptide import into the lumen of the endoplasmic reticulum as a consequence o f a viral infection. We suggest that the increased supply of peptides for a ssembly with MHC class I molecules in flavivirus-infected cells accounts fo r the upregulation of MHC class I cell surface expression with the biologic al consequence of viral evasion of natural killer cell recognition,