Interferon-independent Increases in Class I Major Histocompatibility Complex Antigen Expression Follow Flavivirus Infection

Department of Microbiology, John Curtin School of Medical Research, Australian National University, Canberra, A.C.T. 2600, Australia 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- (IFN- ) secretion, as anti-IFN- antibodies partially inhibited the WNV-induced increase but totally prevented increases caused by the addition of (i) pure IFN- , (ii) IFN- -containing supernatants from WNV-infected mouse embryo fibroblasts (MEF), or (iii) polyinosinic-polycytidylic acid. Actinomycin D treatment of MEF, which inhibited mRNA synthesis by >90% as determined by [ 3 H]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. Keywords: flavivirus, MHC, class I, interferons Present address: Department of Anatomy, University of Sydney, New South Wales 2006, Australia. Received 11 January 1988; accepted 15 June 1988.