The nucleotide sequence of cDNA from a high-passage, cell culture-adapted variant of hepatitis A virus strain HM175 was compared with the previously determined sequences of wild-type virus and two other cell culture-adapted variants. A total of 42 nucleotide changes were detected when the sequence was compared with wild-type virus. Five of these changes were common to all cell culture-adapted strains and a further two changes were shared by the strains that had experienced the greatest number of cell culture passages. The mutations were distributed throughout the genome coding for amino acid substitutions in regions 2B, 2C and 3D with silent changes in 1C and the 5′ non-coding region. The possible relevance of these mutations to cell culture adaptation and attenuation is discussed.


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