Major histocompatibility complex class I (MHC-I) induction by West Nile virus: involvement of 2 signaling pathways in MHC-I up-regulation.
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.
Cheng
Ying
Y
Department of Pathology, School of Biomedical Sciences and Institute for Biomedical Research, Faculty of Medicine, University of Sydney, Sydney, Australia.
King
Nicholas J C
NJ
Kesson
Alison M
AM
D000818:Animals; D002522:Chlorocebus aethiops; D005347:Fibroblasts / Q000276:immunology / Q000821:virology; D005786:Gene Expression Regulation / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D007370:Interferon Type I / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D017471:Receptors, Interferon / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D014709:Vero Cells; D014902:West Nile virus / Q000254:growth & development* / Q000276:immunology*
D015395:Histocompatibility Antigens Class I; D007370:Interferon Type I; D017471:Receptors, Interferon