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Genotype-Specific Evolution of Hepatitis E Virus

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Brayne, AB 
Dearlove, BL 
Lester, JS 
Kosakovsky Pond, SL 
Frost, SDW 

Abstract

Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis globally. HEV comprises four genotypes with different geographic distributions and host ranges. We utilize this natural case-control study for investigating the evolution of zoonotic viruses compared to single-host viruses, using 244 near-full-length HEV genomes. Genome-wide estimates of the ratio of nonsynonymous to synonymous evolutionary changes (dN/dS ratio) located a region of overlapping reading frames, which is subject to positive selection in genotypes 3 and 4. The open reading frames (ORFs) involved have functions related to host-pathogen interaction, so genotype-specific evolution of these regions may reflect their fitness. Bayesian inference of evolutionary rates shows that genotypes 3 and 4 have significantly higher rates than genotype 1 across all ORFs. Reconstruction of the phylogenies of zoonotic genotypes demonstrates significant intermingling of isolates between hosts. We speculate that the genotype-specific differences may result from cyclical adaptation to different hosts in genotypes 3 and 4.IMPORTANCE Hepatitis E virus (HEV) is increasingly recognized as a pathogen that affects both the developing and the developed world. While most often clinically mild, HEV can be severe or fatal in certain demographics, such as expectant mothers. Like many other viral pathogens, HEV has been classified into several distinct genotypes. We show that most of the HEV genome is evolutionarily constrained. One locus of positive selection is unusual in that it encodes two distinct protein products. We are the first to detect positive selection in this overlap region. Genotype 1, which infects humans only, appears to be evolving differently from genotypes 3 and 4, which infect multiple species, possibly because genotypes 3 and 4 are unable to achieve the same fitness due to repeated host jumps.

Description

Keywords

evolution, evolutionary biology, genotypic identification, hepatitis E virus, positive selection

Journal Title

Journal of Virology

Conference Name

Journal ISSN

0022-538X
1098-5514

Volume Title

91

Publisher

American Society for Microbiology
Sponsorship
Medical Research Council (MR/J013862/1)
This work was funded in part by a Medical Research Council Methodology Research Programme grant (MR/J013862/1) to SDWF, as well as by the Department of Pathology at the Unive rsity of Cambridge. SLKP and HyPhy development was supported by the US National Institutes of Health (grants GM093 939 and GM110749).