Ribavirin Can Be Mutagenic for Arenaviruses

• DOI: 10.1128/jvi.00614-11
• Publication Date: 2011-05-12T04:29:37Z
• Authors: Héctor Moreno; Isabel Gallego; Noemí Sevilla; Juan Carlos de la...; Esteban Domingo; Verónica Martín
• Keywords: 0303 health sciences; 03 medical and health sciences; Base Sequence; Reverse Transcriptase Polymerase Chain Reaction; Cricetinae; Ribavirin; Animals; Arenavirus; Antiviral Agents; Cell Line; DNA Primers; 3. Good health

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 the purine nucleoside analogue ribavirin (1- β - d -ribofuranosyl-1- H -1,2,4-triazole-3-carboxamide) is only antiviral treatment currently available for arenavirus infections. However, mechanism action against arenaviruses remains unknown. Here we document that mutagenic prototypic lymphocytic choriomeningitis virus (LCMV) in cell culture. The activity on LCMV was observed under single- multiple-passage regimes could not be accounted by a decrease intracellular GTP pool promoted ribavirin-mediated inhibition inosine monophosphate dehydrogenase (IMPDH). Our findings suggest might exerted, at least partially, lethal mutagenesis. Implications antiarenavirus therapy discussed.