Hijacking hepatitis C viral replication with a non-coding replicative RNA.
Antiviral Res
; 87(1): 9-15, 2010 Jul.
Article
em En
| MEDLINE
| ID: mdl-20382185
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antivirais
/
Replicação Viral
/
Hepacivirus
/
RNA não Traduzido
Limite:
Humans
Idioma:
En
Revista:
Antiviral Res
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
França