The role of tumor necrosis factor in modulating responses of murine embryo fibroblasts by flavivirus, West Nile

被引:25
作者
Cheng, Y
King, NJC
Kesson, AM
机构
[1] Childrens Hosp, Dept Virol & Microbiol, Westmead, NSW 2145, Australia
[2] Univ Sydney, Fac Med, Inst Biomed Res, Sydney, NSW 2006, Australia
[3] Univ Sydney, Sch Biomed Sci, Dept Pathol, Sydney, NSW 2006, Australia
[4] Univ Sydney, Dept Paediat & Child Hlth, Sydney, NSW 2006, Australia
基金
英国医学研究理事会;
关键词
West Nile virus; flavivirus; major histocompatibility complex; nuclear factor-kappa B; tumor necrosis factor;
D O I
10.1016/j.virol.2004.06.050
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Murine embryo fibroblasts (MEF) transcribe tumor necrosis factor (TNF) mRNA and secrete soluble TNF in response to infection by West Nile virus (WNV) and TNF was demonstrated to be protective against WNV infection in vitro. TNF is not required for the WNV-induced upregulation of MHC-I expression on MEF, as TNF deficiency did not affect the upregulation of major histocompatibility complex class I (MHC-I) by WNV Furthermore, NF-kappaB was activated by WNV in TNF-deficient MEF, demonstrating that WNV induces NF-kappaB activation in a TNF-independent manner. The subunits of NF-kappaB activated by TNF and WNV differed, WNV-activated a p65/p50 NF-kappaB complex while TNF-activated NF-kappaB was composed of p65, p50, and c-Rel. Furthermore, TNF-induced activation of NF-kappaB occurred earlier than WNV-induced NF-kappaB activation. The data demonstrate that WNV infection of MEF is associated with TNF production, but the WNV-induced activation of NF-kappaB and subsequent upregulation of MHC-I by WNV is TNF-independent. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:361 / 370
页数:10
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