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

Abstract

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-κB was activated by WNV in TNF-deficient MEF, demonstrating that WNV induces NF-κB activation in a TNF-independent manner. The subunits of NF-κB activated by TNF and WNV differed, WNV-activated a p65/p50 NF-κB complex while TNF-activated NF-κB was composed of p65, p50, and c-Rel. Furthermore, TNF-induced activation of NF-κB occurred earlier than WNV-induced NF-κB activation. The data demonstrate that WNV infection of MEF is associated with TNF production, but the WNV-induced activation of NF-κB and subsequent upregulation of MHC-I by WNV is TNF-independent. © 2004 Elsevier Inc. All rights reserved.