Major histocompatibility complex class I (MHC-I) induction by West Nile virus: involvement of 2 signaling pathways in MHC-I up-regulation

J Infect Dis. 2004 Feb 15;189(4):658-68. doi: 10.1086/381501. Epub 2004 Feb 5.

Abstract

Type 1 interferon (IFN) receptor gene knockout (IFNAR(-/-)) mouse embryo fibroblasts (MEFs) are more susceptible to and productive of West Nile virus (WNV) and produce less type 1 IFN than WNV-infected wild-type (wt) MEFs. WNV infection of IFNAR(-/-) MEFs induced activation of a p65/p50 heterodimer of nuclear factor (NF)- kappa B and up-regulation of cell-surface expression of major histocompatibility complex class I (MHC-I) molecules. WNV infection of wt MEFs resulted in a greater up-regulation of MHC-I than did infection of IFNAR(-/-) MEFs because of the action of endogenous type 1 IFN production. IFN- beta -treatment of wt MEFs did not activate NF- kappa B but did up-regulate cell-surface MHC-I expression. The WNV-induced NF- kappa B activation was partially abrogated by the serine protease inhibitor N-benzoyl-l-tosyl-l-phenylalanine, which also abrogated the up-regulation of MHC-I. Thus, we demonstrate 2 pathways for WNV-induced up-regulation of MHC-I, a WNV-induced NF- kappa B-dependent, IFN-independent pathway and an NF- kappa B-independent, IFN-dependent pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chlorocebus aethiops
  • Fibroblasts / immunology
  • Fibroblasts / virology
  • Gene Expression Regulation / immunology*
  • Histocompatibility Antigens Class I / genetics*
  • Interferon Type I / immunology
  • Mice
  • Mice, Knockout
  • Receptors, Interferon / deficiency
  • Receptors, Interferon / genetics
  • Receptors, Interferon / immunology
  • Signal Transduction / immunology
  • Vero Cells
  • West Nile virus / growth & development*
  • West Nile virus / immunology*

Substances

  • Histocompatibility Antigens Class I
  • Interferon Type I
  • Receptors, Interferon