The interferon-inducible RNA helicase, mda-5, is involved in measles virus-induced expression of antiviral cytokines

Activation of host cell antiviral responses is mediated by receptors detecting the presence of viruses. Here we have studied the role of double-stranded RNA (dsRNA) binding molecules melanoma differentiation-associated gene 5 (mda-5), retinoic acid inducible gene I (RIG-I), and Toll-like receptor 3 (TLR3) in measles virus (MV)-induced expression of antiviral cytokines and chemokines in human A549 lung epithelial cells and human umbilical vein endothelial cells (HUVECs). We show that MV infection results in the activation of mda-5, RIG-I, and TLR3 gene expression that is followed by high expression of interferon (IFN)-β, interleukin (IL)-28 and IL-29, CCL5, and CXCL10 genes. We also demonstrate that IFN-α and IFN-β upregulate mda-5, RIG-I, and TLR3 gene expression in epithelial and endothelial cell lines. Forced expression of mda-5, but not that of RIG-I or TLR3, leads to enhanced IFN-β promoter activity in MV-infected A549 cells. Our results suggest that IFN-inducible mda-5 is involved in MV-induced expression of antiviral cytokines.