Japanese Encephalitis Virus Utilizes the Canonical Pathway To Activate NF-κB but It Utilizes the Type I Interferon Pathway To Induce Major Histocompatibility Complex Class I Expression in Mouse Embryonic Fibroblasts

Immunobiology of Japanese Encephalitis Virus

“…Flavivirus-induced up-regulation of MHC-I cell surface expression is, at least in part, IFN-independent (Abraham et al, 2010;Kesson & King, 2001;Mullbacher & Lobigs, 1995), and also includes that of non-classical MHC-I (Abraham et al, 2008). Although the physiological relevance of this phenomenon in virus transmission remains unclear, it has been proposed that the process may contribute to reduced NK cell activity, which is inhibited by engagement with MHC-I by NK cell inhibitory receptors (Hershkovitz et al, 2008;Momburg et al, 2001).…”

“…In the case of JEV infection, RIG-1-dependent IRF-3 and phosphatidylinositol-3 kinase-dependent NF-B activation is essential for IFN production . NF-B-dependent and NF-B-independent mechanisms of IFN induction after JEV infection have been suggested by Abraham et al (2010). Binding of IFN to its cognate receptor at the cell surface triggers a signalling cascade, the Janus kinasesignal transducer and activation of transcription (Jak-Stat) pathway, ultimately triggering IFN-stimulated response element and expression of IFN-stimulated genes (ISGs).…”

Japanese Encephalitis Virus: Innate and Adaptive Immunity

“…The absence of MHC-II induction during JEV infection could be important because it may lead to the initiation of an immune response which is different from other flaviviral infections that induce the expression of MHC-II molecules. Again, in contrast to WNV, the use of knockout MEFs showed that JEV-mediated induction of classical MHC-I molecules remained unaffected in NF-κB defective cells but was completely dependent on type I IFNs (Abraham et al, 2010). In contrast to classical MHC molecules, the nonclassical MHC molecules do not belong to a single group of structurally and functionally homologous proteins and normally have lower cell surface expression.…”

“…Using IKK1 -/-, IKK2 -/-, IKK3 -/-and IKK1 -/-IKK2 -/-double mutant as well as RelA -/-cRel -/-p50 -/--triple mutant mouse embryonic fibroblasts infected with JEV, it has been shown that JEV activates the classical pathway of NF-κB activation in a IKK2-and IKK3-but not IKK1-dependent manner that involved RelA and p50 complexes. NF-κB dependent and independent mechanisms also critically determined type I IFN induction in JEV infected MEFs (Abraham et al, 2010). In addition to its involvement in immune responses, apoptosis and the cell cycle (Bonizzi and Karin, 2004), NF-κB has been shown to play a major role in flavivirus-mediated induction of MHC-I (Cheng et al, 2004).…”

“…H2-T10 (Abraham et al, 2010). Panel C represents IL-2 secretion from G8, T cell clone upon activation with JEV infected H6 hepatoma cells.…”