a, b, An infectious chimaeric virus was constructed from JFH1 and J6CF as shown in a; the numbers in brackets indicate the location in the virion (nucleotides) that the miRNA binds. The Huh7-cell subclone Huh7.5.1c2 was transfected with either miR-196 or miR-448, or with the mutant miR-196* and miR-448* harbouring a compensatory mutation in the seed sequence as outlined in a. Transfected Huh7.5.1c2 cells were infected with JFH1(D183) (ref. 23) or chimaeric J6/JFH, and HCV RNA was quantified by qPCR after 24 or 60 h post infection, respectively, during the phase of exponential viral RNA amplification, to accommodate the difference in replication kinetics between the two viruses (error bars, means ± s.e.m. of 8 independent experiments; P values are from paired Student’s t-tests).