HEV adapts to in vitro culture but shows limited mutagenesis in the humanized mouse model. Genomic differences after in vitro and in vivo passage of HEV derived from HEV0069 feces are depicted per ORF. The HEV0069 feces isolate is used as reference sequence and the nucleotide and amino acid sequence differences are highlighted in yellow and red, respectively. nt, nucleotide; aa, amino acid; ORF, open reading frame; Green, no change in amino acid sequence; Red, change in amino acid sequence; Yellow, nucleotide differences with respect to feces nucleotide sequence. Nucleotide abbreviations; M = A,C; S = G,C; W = A,T; Y = T,C. HEV0069 sequence is relative to HEV wbGER27 (GenBank accession number: FJ705359).