Transcriptional regulation of major histocompatibility complex class I by flavivirus West Nile is dependent on NF-kappaB activation.
Infection by the flavivirus West Nile (WNV) is associated with a virus-specific increase of major histocompatibility complex class I (MHC-I) molecules on the cell surface of diploid vertebrate cells. The increased MHC-I cell surface expression is functional and is associated with increased susceptibility to secondary WNV-immune and alloimmune cytotoxic T cells. WNV-induced up-regulation of cell surface MHC-I expression is associated with NF-kappaB activation and increased transcription of MHC-I mRNA. WNV infection increases luciferase activity of RAWa4 long terminal repeat (LTR) cells, which are transfected stably with a plasmid containing 2 NF-kappaB binding sites, the human immunodeficiency virus LTR linked to a luciferase reporter gene. The NF-kappaB-induced complexes are a p50/p65 heterodimer and another faster migrating species containing p50 homodimers. WNV-induced activation of NF-kappaB and the up-regulation of MHC-I were blocked by the protein kinase C inhibitor H-7 and salicylate, both of which block phosphorylation of inhibitor kappaB.
Kesson
A M
AM
Department of Virology and Microbiology, Children's Hospital at Westmead, Westmead, Australia. alisonk2@chw.edu.au
King
N J
NJ
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D005260:Female; D005347:Fibroblasts / Q000276:immunology / Q000821:virology; D005786:Gene Expression Regulation; D005805:Genes, MHC Class I; D017930:Genes, Reporter; D016325:HIV Long Terminal Repeat; D008156:Luciferases / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D016328:NF-kappa B / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D014901:West Nile Fever / Q000276:immunology / Q000821:virology*; D014902:West Nile virus / Q000276:immunology*
D016328:NF-kappa B; D012333:RNA, Messenger; D008156:Luciferases