Evidence that a mechanism for efficient flavivirus budding upregulates MHC class I

An appealing hypothesis for the biological role of flavivirus-induced, interferon-independent, upregulation of MHC class I on the surface of infected cells is that of viral immune evasion from NK cell recognition. Here we show that a mechanism for efficient flavivirus morphogenesis interferes with the MHC class I pathway, using a flavivirus budding mutant and recombinant expression of wild-type and mutant forms of the flavivirus structural proteins. We propose that the phenomenon of flavivirus-mediated MHC class I upregulation is a by-product of a unique assembly strategy evolved by flaviviruses and therefore did not evolve primarily as an immune escape mechanism for virus growth in the vertebrate host.