The exonuclease ISG20 is directly induced by synthetic dsRNA via NF-κB and IRF1 activation

Abstract

Many interferon (IFN)-stimulated genes are also induced by double-stranded RNA (dsRNA), a component closely associated with the IFN system in the context of virushost interactions. Recently, we demonstrated that the IFN-induced 3 0 -5 0 exonuclease ISG20 possesses antiviral activities against RNA viruses. Here we show that ISG20 induction by synthetic dsRNA (pIpC) is stronger and faster than its induction by IFN. Two families of transcription factors are implicated in the transcriptional activation of ISG20 by dsRNA. Initially, the NF-kB factors p50 and p65 bind and activate the kB element of the Isg20 promoter. This is followed by IRF1 binding to the ISRE. As pIpC often induces protein movements in the cells, we questioned whether it could influence ISG20 localization. Interestingly and contrary to IFN, dsRNA induces a nuclear matrix enrichment of the ISG20 protein. dsRNA induction of ISG20 via NF-kB and its antiviral activity led us to suggest that ISG20 could participate in the cellular response to virus infection.

Polysaccharide Purified fromGanoderma lucidumInduces Gene Expression Changes in Human Dendritic Cells and Promotes T Helper 1 Immune Response in BALB/c Mice

“…Moreover, the TATA-less Isg20 promoter contains one E-box and putative NF-B and Sp-1 binding sites, suggesting that it could be induced by other stimuli. ISG20 has an antiviral activity, supporting the idea that it might represent a novel antiviral pathway (Espert et al, 2004). G. lucidum has been reported to have antiviral activity .…”

Expression regulation and functional characterization of a novel interferon inducible gene Gig2 and its promoter

“…Although further deletion assay revealed an essential role of ISREs in the induction of fish type II IFN inducible genes (Castro et al, 2008), many mammalian IFN inducible genes have both ISRE and GAS sites, and GAS seems responsible for IFN-␥ induction. There are also some exceptions, for example, a unique ISRE in the TATAless human ISG20 promoter confers IRF1-mediated responsiveness to both type I IFN and type II IFN (Espert et al, 2004;Gongora et al, 2000).…”

RhoJ/TCL Regulates Endothelial Motility and Tube Formation and Modulates Actomyosin Contractility and Focal Adhesion Numbers

“…The RhoJ knockdown efficiently knocked down RhoJ protein levels ( Figure 2E) but did not alter the levels of Cdc42, Rac1, or RhoA in endothelial cells (supplemental Figure IV). The absence of any interferon response at duplex concentrations used for any of the various assays was confirmed by monitoring expression of the interferon inducible genes 2Ј,5Ј-oligoadenylate synthetase 1 22 and IFN-stimulated gene of 20 kDa 23 (data not shown).…”