FIG 3.

Mutation frequency in influenza virus populations treated with nucleoside analogs. MDCK cells were infected with influenza A/PR8/34 (H1N1) virus at an MOI of 0.1 in drug-containing medium. Supernatants were harvested at 24 h postinfection. A 957-base fragment of the HA gene was amplified and cloned. Between 51 and 110 clones from each sample were sequenced, and mutations were identified. Overall mutation frequencies are expressed per 10⁴ bases sequenced. Wild-type bases are on the left in each table. Specific mutation types are expressed per 10⁴ wild-type bases sequenced. Mutations identified in multiple clones were counted once. A chi-square test was used to determine the statistical significance of the differences in total mutation frequency for each mutation type relative to the no-drug control. *, P < 0.05; **, P < 0.005. Statistically significant increases are highlighted by shading. (A) Each nucleoside analog compared to a no-drug control. (B) Treatment with multiple concentrations of ribavirin.