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Article Dans Une Revue Antiviral Research Année : 2010

Hijacking hepatitis C viral replication with a non-coding replicative RNA.

Résumé

The current treatments used against RNA viruses have a limited efficacy and are often hampered by the induction of side-effects. The specific delivery of antiviral proteins in infected cells should increase their efficiency and reduce their impact on healthy cells. Here, we describe the development of a new approach which takes advantage of the viral replication machinery to specifically target the antiviral protein expression to the infected cells. The strategy is based on the delivery of a non-coding (-)RNA carrying the structures required for the binding of the viral replication complex and the complementary sequence of an antiviral gene. The viral replication complex replicates the (-)RNA similarly to the viral genome to give a coding (+)RNA from which the antiviral protein will be expressed. As non-infected cells do not express the replication complex, this specific machinery can be used to target virus-infected cells without affecting healthy cells. We show that this approach can be successfully applied to the hepatitis C virus. In both replicon-harboring cells (genotype 1b) and JFH-1 infected cells (genotype 2a), nrRNAs induced a strong decrease in genomic RNA and viral protein NS5A. These effects were correlated with a strong activation of several interferon-stimulating genes.

Dates et versions

hal-00522680 , version 1 (01-10-2010)

Identifiants

Citer

Juliette Bitard, Gaëlle Chognard, Estelle Dumas, Julie Rumi, Cyril Masante, et al.. Hijacking hepatitis C viral replication with a non-coding replicative RNA.. Antiviral Research, 2010, 87 (1), pp.9-15. ⟨10.1016/j.antiviral.2010.04.003⟩. ⟨hal-00522680⟩

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