title: Ribavirin can be mutagenic for arenaviruses.
abstract: Arenaviruses include several important human pathogens, and there are very limited options of preventive or therapeutic interventions to combat these viruses. An off-label use of the purine nucleoside analogue ribavirin (1-β-d-ribofuranosyl-1-H-1,2,4-triazole-3-carboxamide) is the only antiviral treatment currently available for arenavirus infections. However, the ribavirin antiviral mechanism action against arenaviruses remains unknown. Here we document that ribavirin is mutagenic for the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) in cell culture. The mutagenic activity of ribavirin on LCMV was observed under single- and multiple-passage regimes and could not be accounted for by a decrease of the intracellular GTP pool promoted by ribavirin-mediated inhibition of inosine monophosphate dehydrogenase (IMPDH). Our findings suggest that the antiviral activity of ribavirin on arenaviruses might be exerted, at least partially, by lethal mutagenesis. Implications for antiarenavirus therapy are discussed.
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Consejo Superior de Investigaciones Científicas (CSIC), Campus de Cantoblanco, 28049 Madrid, Spain.
authors.forename: Héctor
authors.initials: H
authors.lastname: Moreno
authors.forename: Isabel
authors.initials: I
authors.lastname: Gallego
authors.forename: Noemí
authors.initials: N
authors.lastname: Sevilla
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: de la Torre
authors.forename: Esteban
authors.initials: E
authors.lastname: Domingo
authors.forename: Verónica
authors.initials: V
authors.lastname: Martín
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D018050:Arenavirus / Q000187:drug effects*; D001483:Base Sequence; D002460:Cell Line; D006224:Cricetinae; D017931:DNA Primers; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012254:Ribavirin / Q000494:pharmacology*
chemical_list: D000998:Antiviral Agents; D017931:DNA Primers; D012254:Ribavirin