title: Interferon-induced exonuclease ISG20 exhibits an antiviral activity against human immunodeficiency virus type 1.
abstract: Interferons (IFNs) encode a family of secreted proteins that provide the front-line defence against viral infections. It was recently shown that ISG20, a new 3'-->5' exoribonuclease member of the DEDD superfamily of exonucleases, represents a novel antiviral pathway in the mechanism of IFN action. In this report, it was shown that ISG20 expression is rapidly and strongly induced during human immunodeficiency virus type 1 (HIV-1) infection. In addition, it was demonstrated that the replication kinetics of an HIV-1-derived virus expressing the ISG20 protein (HIV-1(NL4-3ISG20)) was delayed in both CEM cells and peripheral blood mononuclear cells. No antiviral effect was observed in cells overexpressing a mutated ISG20 protein defective in exonuclease activity, suggesting that the antiviral effect was due to the exonuclease activity of ISG20. Paradoxically, despite the antiviral activity of ISG20 protein, virus rescue observed in HIV-1(NL4-3ISG20)-infected cells was not due to mutation or partial deletion of the ISG20 transgene, suggesting that the virus was able to counteract the cellular defences. In addition, HIV-1-induced apoptosis was significantly reduced in HIV-1(NL4-3ISG20)-infected cells suggesting that emergence of HIV-1(NL4-3ISG20) was associated with the inhibition of HIV-1-induced apoptosis. Altogether, these data reflect the ineffectiveness of virus replication in cells overexpressing ISG20 and demonstrate that ISG20 represents a new factor in the IFN-mediated antiviral barrier against HIV-1.
authors: CNRS, UMR-5160, EFS, 240 avenue Emile Jeanbrau, 34094 Montpellier Cedex 5, France.
authors: Lucile
authors: L
authors: Espert
authors: CNRS, UMR-5160, EFS, 240 avenue Emile Jeanbrau, 34094 Montpellier Cedex 5, France.
authors: Geneviève
authors: G
authors: Degols
authors: Institut de Genetique Humaine, CNRS, UPR-1142, 141 rue de la Cardonille, 34396 Montpellier Cedex 5, France.
authors: Yea-Lih
authors: YL
authors: Lin
authors: Laboratoire d'Immunologie, Hôpital St-Eloi, 80 Avenue A. Fliche, 34295 Montpellier Cedex 5, France.
authors: Thierry
authors: T
authors: Vincent
authors: Institut de Genetique Humaine, CNRS, UPR-1142, 141 rue de la Cardonille, 34396 Montpellier Cedex 5, France.
authors: Monsef
authors: M
authors: Benkirane
authors: CNRS, UMR-5160, EFS, 240 avenue Emile Jeanbrau, 34094 Montpellier Cedex 5, France.
authors: Nadir
authors: N
authors: Mechti
mesh_terms: D017209:Apoptosis; D002460:Cell Line; D018920:Coculture Techniques; D015536:Down-Regulation; D004790:Enzyme Induction; D005092:Exonucleases / Q000096:biosynthesis / Q000502:physiology*; D005095:Exoribonucleases; D015967:Gene Expression Regulation, Viral; D015658:HIV Infections / Q000201:enzymology* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007372:Interferons; D009154:Mutation; D014779:Virus Replication
chemical_list: D007372:Interferons; D005092:Exonucleases; D005095:Exoribonucleases; C112346:ISG20 protein, human