Cytokine-Independent Upregulation of MDA5 in Viral Infection

Yount JS, Moran TM, Lopez CB
Source: J Virol
Publication Date: (2007)
Issue: 81(13): 7316-9
Research Area:
Cancer Research/Cell Biology
Cells used in publication:
Species: human
Tissue Origin: blood
Nucleofectorâ„¢ I/II/2b
The RNA helicases RIG-I and MDA5 detect virus infection of dendritic cells (DCs) leading to cytokine induction. Maximal sensitivity for virus detection by these helicases is obtained after their upregulation, which is thought to occur primarily through type I interferon (IFN) signaling. Here we demonstrate that in response to paramyxovirus infection, RIG-I upregulation requires type I IFN whereas MDA5 expression is increased by Sendai virus infection independently of signaling mediated by type I IFN, STAT1, tumor necrosis factor alpha, or NF-kappaB. This MDA5 upregulation is largely lost in IRF3 knockout DCs and is achieved in type I IFN-deficient cells expressing constitutively active IRF3.