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This Article Full Text Full Text (PDF) Supplementary Data All Versions of this Article: vir.0.008821-0v1 90/7/1659    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via CrossRef Google Scholar Articles by Romero-López, C. Articles by Berzal-Herranz, A. PubMed PubMed Citation Articles by Romero-López, C. Articles by Berzal-Herranz, A. Agricola Articles by Romero-López, C. Articles by Berzal-Herranz, A.

Inhibition of hepatitis C virus replication and internal ribosome entry site-dependent translation by an RNA molecule

Instituto de Parasitología y Biomedicina ‘López-Neyra’, CSIC, Parque Tecnológico de Ciencias de la Salud, Avda del Conocimiento s/n, Armilla, 18100 Granada, Spain

Correspondence
Alfredo Berzal-Herranz
Aberzalh{at}ipb.csic.es

Hepatitis C virus (HCV) protein synthesis is mediated by a highly conserved internal ribosome entry site (IRES), mostly located at the 5' untranslatable region (UTR) of the viral genome. The translation mechanism is different from that used by cellular cap-mRNAs, making IRESs an attractive target site for new antiviral drugs. The present work characterizes a chimeric RNA molecule (HH363-50) composed of two inhibitors: a hammerhead ribozyme targeting position 363 of the HCV genome and an aptamer directed towards the essential stem–loop structure in domain IV of the IRES region (which contains the translation start codon). The inhibitor RNA interferes with the formation of a translationally active complex, stalling its progression at the level of 80S particle formation. This action is likely related to the effective and specific blocking of HCV IRES-dependent translation achieved in Huh-7 cells. The inhibitor HH363-50 also reduces HCV RNA levels in a subgenomic replicon system. The present findings suggest that HH363-50 could be an effective anti-HCV compound and highlight the possibilities of antiviral agents based on RNA molecules.

A supplementary figure showing the intracellular stability of HH363-50 and a table of primer sequences are available with the online version of this paper.