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Genotype-Specific Evolution of Hepatitis E Virus.
J Virol. 2017 05 01; 91(9)JV

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.

Authors+Show Affiliations

University of Cambridge, Cambridge, United Kingdom.University of Cambridge, Cambridge, United Kingdom.University of Cambridge, Cambridge, United Kingdom.Temple University, Philadelphia, Pennsylvania, USA.University of Cambridge, Cambridge, United Kingdom sdf22@cam.ac.uk.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

28202767

Citation

Brayne, Adam B., et al. "Genotype-Specific Evolution of Hepatitis E Virus." Journal of Virology, vol. 91, no. 9, 2017.
Brayne AB, Dearlove BL, Lester JS, et al. Genotype-Specific Evolution of Hepatitis E Virus. J Virol. 2017;91(9).
Brayne, A. B., Dearlove, B. L., Lester, J. S., Kosakovsky Pond, S. L., & Frost, S. D. W. (2017). Genotype-Specific Evolution of Hepatitis E Virus. Journal of Virology, 91(9). https://doi.org/10.1128/JVI.02241-16
Brayne AB, et al. Genotype-Specific Evolution of Hepatitis E Virus. J Virol. 2017 05 1;91(9) PubMed PMID: 28202767.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genotype-Specific Evolution of Hepatitis E Virus. AU - Brayne,Adam B, AU - Dearlove,Bethany L, AU - Lester,James S, AU - Kosakovsky Pond,Sergei L, AU - Frost,Simon D W, Y1 - 2017/04/13/ PY - 2016/11/15/received PY - 2017/01/31/accepted PY - 2017/2/17/pubmed PY - 2017/5/16/medline PY - 2017/2/17/entrez KW - evolution KW - evolutionary biology KW - genotypic identification KW - hepatitis E virus KW - positive selection JF - Journal of virology JO - J Virol VL - 91 IS - 9 N2 - 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. SN - 1098-5514 UR - https://www.unboundmedicine.com/medline/citation/28202767/Genotype_Specific_Evolution_of_Hepatitis_E_Virus_ L2 - https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/28202767/ DB - PRIME DP - Unbound Medicine ER -