Year: 2007
Type: article
Abstract: CHRISTOPER POPE ELCOdsRNA is an important regulator of gene induction.The cellular response to dsRNA is mediated through either toll-like receptor 3 (TLR3) or the RNA helicases, RIG-I and mda5.While TLR3 and RIG-I/mda5 recognize dsRNA in different cellular compartments, both can signal to activate the transcription factors IRF-3 and NFκB.Both transcription factors, in turn, regulate the expression of hundreds of genes.This dissertation contains the following contributions to the field of dsRNA signaling:1. Sendai virus, a negative-strand RNA virus, does not induce cellular genes through TLR3, rather RIG-I is required for the induction of ISG56 by SeV.In contrast, adding dsRNA to the culture media leads to only TLR3-mediated gene induction.2. STAT1-null, U3A cells do not respond to dsRNA added to the media as the result of low TLR3 expression.Expression of STAT1 in U3A cells allows them to respond to interferon, but not dsRNA.However, pre-treatment of STAT1-restored U3A cells with interferon-γ or interferon-β induces TLR3 expression, and makes the cells responsive to dsRNA.This result shows that stimulation with interferons, by inducing TLR3, can make cells, otherwise unresponsive to dsRNA, responsive.
Author: Christopher P. Elco
Institution: Case Western Reserve University
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2521293483