Infection of tertiary-passaged mouse embryo fibroblasts by four flaviviruses, West Nile (WNV), Kunjin,
Murray Valley encephalitis and
Japanese B encephalitis, resulted in a six- to 10-fold increase in the expression of individual H-2K and H-2D class I major histocompatibility complex (MHC)
antigens 16 to 48 h after
infection. The mechanism(s) by which flaviviruses increased
antigen expression has not been fully elucidated, but appears to be mediated partly independently of
interferon-beta (IFN-beta) secretion, as anti-IFN-alpha beta
antibodies partially inhibited the WNV-induced increase but totally prevented increases caused by the addition of (i) pure IFN-beta, (ii) IFN-beta-containing supernatants from WNV-infected mouse embryo fibroblasts (MEF), or (iii)
polyinosinic-polycytidylic acid.
Actinomycin D treatment of MEF, which inhibited
mRNA synthesis by greater than 90% as determined by [3H]
uridine uptake, totally inhibited the increased MHC expression caused by
WNV infection. Thus, the increase in class I MHC
antigen expression following
infection is dependent upon cellular
RNA synthesis.