Transcriptional regulation of major histocompatibility complex class I by flavivirus West Nile is dependent on NF-κB activation

Abstract

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-κB 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-κB binding sites, the human immunodeficiency virus LTR linked to a luciferase reporter gene. The NF-κB-induced complexes are a p50/p65 heterodimer and another faster migrating species containing p50 homodimers. WNV-induced activation of NF-κB 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 κB. © 2001 by the Infectious Diseases Society of America.