The genetic divergences of codon usage shed new lights on transmission of hepatitis E virus from swine to human.

Hepatitis E virus (HEV) is an important pathogen causing public health burden. Swine has been recognized as a main reservoir. Interestingly, genotype 1 HEV only infects human; whereas genotype 3 and 4 are zoonotic. However, there is a lack of in-depth understanding in respect to the transmission from swine to human. Codon usage patterns generally participate in viral survival and fitness towards its hosts. We have analyzed codon usage patterns of the three open reading frames (ORFs) for 243 full-length genomes of HEV genotypes 1, 3 and 4. The divergence of synonymous codon usage patterns is different in each ORF for genotypes 1, 3 and 4, but the genotype-specific codon usage bias in genotype 1 is stronger than those of genotypes 3 and 4. In respect to genotypes 3 and 4, compared with strains isolated from human, HEV isolated from swine shows appreciable variation in adaptation of codon usages to human or swine. These results may help to understand the transmission and host adaptation of HEV genotypes 3 and 4 from swine to human.