Hijacking hepatitis C viral replication with a non-coding replicative RNA
Antiviral Research. 2010-07-01; 87(1): 9-15
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Bitard J(1), Chognard G, Dumas E, Rumi J, Masante C, Mahias K, Astier-Gin T, Ventura M.
(1)UMR CNRS, IFR, Université Victor Segalen Bordeaux, France.
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.
2010 Elsevier B.V. All rights reserved.