Using codon usage analysis to speculate potential animal hosts of hepatitis E virus: An exploratory study

Abstract

There has been an increase in the reported number of animals worldwide that carry the hepatitis E virus (HEV). This study aimed to explore potential animal hosts for HEV through codon usage analysis. Full-length HEV sequences of six genotypes as well as codon usage of potential animal hosts were collected. Moreover, nucleotide composition and codon usage bias were compared across HEV genotypes and animal hosts. Based on the analysis for human HEV-1 and humans, the results were basically consistent with epidemiology evidence. Among 17 potential animal hosts, all HEV genotypes exhibited a preference for guanine/cytosine in the third position of synonymous codons. Furthermore, non-human primates and humans have large high-frequency codons identical to HEV in addition to a high correlation of codon fraction with HEV. Some animals in close contact with humans showed high preference for HEV, including cattle, dogs, and rats with HEV-A, cats, dogs, and swine with HEV-C1. Codon usage bias has limited efficiency in determining the hosts for HEV, but it may provide indicative clues for potential animal hosts when combined with experimental and epidemiological evidence.

Keywords: Animal host; Codon usage; Cross-species transmission; Hepatitis E virus.