MHC class I up-regulation by flaviviruses: Immune interaction with unknown advantage to host or pathogen

Abstract

In contrast to many other viruses that escape from cytotoxic T cell recognition by down-regulating major histocompatibility complex class I-restricted antigen presentation, flavivirus infection of mammalian cells upregulates cell surface expression of major histocompatibility complex class I molecules. Two putative mechanisms for flavivirus-induced major histocompatibility complex class I up-regulation, one via activation of the transcription factor NF-κB, the second by augmentation of peptide import into the lumen of the endoplasmic reticulum, are reviewed, and the biological effect of the flavivirus-mediated phenomenon on target cell recognition by natural killer and cytotoxic T cells is addressed. Finally, we speculate on the physiological role of flavivirus-mediated modulation of major histocompatibility complex class I antigen presentation in the context of the biology of flavivirus transmission between the vertebrate host and arthropod vector and suggest that it may represent a strategy for immune evasion from the natural killer cell response or, alternatively, that up-regulation of major histocompatibility complex class I is a by-product of flavivirus replication without significance for virus growth. Show more