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Papers In Press, published online ahead of print February 19, 2003
UMR CNRS 5094, CNRS, Montpellier 34094
Corresponding Author: nadir.mechti{at}ibph.pharma.univ-montp1.fr
Interferons (IFNs) encode a family of secreted proteins that provide the front-line defense against viral infections. Their diverse biological actions are thought to be mediated by the products of specific but usually overlapping sets of cellular genes induced in the target cells. We have recently isolated a new human IFN-induced gene that we have termed ISG20 and which codes for a 3' to 5' exonuclease with specificity for single-stranded RNA and to a lesser extent for DNA. In this report, we demonstrate that ISG20 is involved in the antiviral functions of IFN. In the absence of IFN treatment, ISG20-overexpressing HeLa cells showed resistance to infections by VSV, influenza virus and EMCV (three RNA genomic viruses) but not to the DNA genomic adenovirus. ISG20 specifically interfered with VSV mRNA synthesis and protein production while leaving unaffected the expression of cellular control genes. No antiviral effect was observed in cells overexpressing a mutated ISG20 protein defective in exonuclease activity, demonstrating that the antiviral effects were due to the exonuclease activity of ISG20. In addition, the inactive mutant ISG20 protein, able to inhibit the ISG20 exonuclease activity in vitro, significantly reduced the ability of IFN to block VSV development. Altogether, these data suggested that the antiviral activity of IFN against VSV is partly mediated by ISG20. We thus show that, besides RNase L, ISG20 has an antiviral activity, supporting the idea that it might represent a novel antiviral pathway in the mechanism of IFN action.
J. Biol. Chem, 10.1074/jbc.M209628200
Submitted on September 19, 2002
Revised on February 11, 2003
Accepted on February 19, 2003
ISG20, a new interferon-induced RNase specific for single-stranded RNA, defines an alternative antiviral pathway against RNA genomic viruses
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