Sequence amplification via cell passaging creates spurious signals of positive adaptation in influenza virus H3N2 hemagglutinin

Abstract excerpt

Clinical influenza A virus isolates are frequently not sequenced directly. Instead, a majority of these isolates (~70% in 2015) are first subjected to passaging for amplification, most commonly in non-human cell culture. Here, we find that this passaging leaves distinct signals of adaptation, which can confound evolutionary analyses of the viral sequences. We find distinct patterns of adaptation to Madin-Darby...

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