A single mutation in poliovirus RNA-dependent RNA polymerase confers resistance to mutagenic nucleotide analogs via increased fidelity

摘要: Ribavirin is a nucleotide analog that can be incorporated by viral polymerases, causing mutations allowing base mismatches. It currently used therapeutically as an antiviral drug during hepatitis C virus infections. During the amplification of poliovirus genomic RNA or replicons, error frequency known to increase upon ribavirin treatment. This observation has led hypothesis ribavirin's activity results from catastrophe caused increased mutagenesis genomes. Here, we describe generation ribavirin-resistant serial passage in presence increasing concentrations drug. resistance single amino acid change, G64S, polymerase unresolved portion fingers domain. Compared with wild-type virus, displays fidelity synthesis absence and survival both another mutagen, 5-azacytidine. Ribavirin-resistant represents unusual class resistance: mutagen through fidelity.