A tightly clustered hepatitis E virus genotype 1a is associated with endemic and outbreak infections in Bangladesh.

<h4>Background</h4>Hepatitis E virus (HEV) infection is endemic in Bangladesh and there are occasional outbreaks. The molecular characteristics and pathogenesis of endemic and outbreak HEV strains are poorly understood. We compared the genetic relatedness and virulence associated mutatio...

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Autores principales:	Trang Nguyen Hoa, Saif Ullah Munshi, Khanh Nguyen Ngoc, Chau Le Ngoc, Thanh Tran Thi Thanh, Tahmina Akther, Shahina Tabassum, Nilufa Parvin, Stephen Baker, Motiur Rahman
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4dfe8860760448f2a643367073631555
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spelling	oai:doaj.org-article:4dfe8860760448f2a6433670736315552021-12-02T20:06:32ZA tightly clustered hepatitis E virus genotype 1a is associated with endemic and outbreak infections in Bangladesh.1932-620310.1371/journal.pone.0255054https://doaj.org/article/4dfe8860760448f2a6433670736315552021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0255054https://doaj.org/toc/1932-6203<h4>Background</h4>Hepatitis E virus (HEV) infection is endemic in Bangladesh and there are occasional outbreaks. The molecular characteristics and pathogenesis of endemic and outbreak HEV strains are poorly understood. We compared the genetic relatedness and virulence associated mutations of endemic HEV strains with outbreak strains.<h4>Methods</h4>We analyzed systematically collected serum samples from HEV immunoglobulin M (IgM) positive patients attended at Bangabandhu Sheikh Mujib Medical University, Dhaka from August 2013 to June 2015. HEV RNA positive samples were subjected to whole genome sequencing. Genotype and subtype of the strains were determined by phylogenetic analysis. Virulence associated mutations e.g. acute viral hepatitis (AVH), fulminant hepatic failure (FHF), chronic hepatitis, ribavirin treatment failure (RTF), B and T cell neutralization epitopes were determined.<h4>Results</h4>92 HEV immunoglobulin M (IgM) antibody positive plasma samples (43 in 2013-2014 and 49 in 2014-2015) were studied. 77.1% (70/92) of the samples were HEV RNA positive. A 279 bp open reading frame (ORF) 2 and ORF 3 sequence was obtained from 54.2% (38/70) of the strains. Of these 38 strains, whole genome sequence (WGS) was obtained from 21 strains. In phylogenetic analysis of 38 (279 bp) sequence all HEV sequences belonged to genotype 1 and subtype 1a. Further phylogenetic analysis of 21 HEV WGS, Bangladeshi HEV sequences clustered with genotype 1a sequences from neighboring countries. Within genotype 1a cluster, Bangladesh HEV strains formed a separate cluster with the 2010 HEV outbreak strains from northern Bangladesh. 80.9 to 100% of the strains had A317T, T735I, L1120I, L1110F, P259S, V1479I, G1634K mutations associates AVH, FHF and RTF. Mutations in T cell recognition epitope T3, T5, T7 was observed in 76.1%, 100% and 100% of the strains respectively.<h4>Conclusion</h4>Strains of HEV genotype 1a are dominant in Bangladesh and are associated with endemic and outbreak of HEV infection. HEV isolates in Bangladesh have high prevalence of virulence associated mutations and mutation which alters antigenicity to B and T cell epitopes.Trang Nguyen HoaSaif Ullah MunshiKhanh Nguyen NgocChau Le NgocThanh Tran Thi ThanhTahmina AktherShahina TabassumNilufa ParvinStephen BakerMotiur RahmanPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 7, p e0255054 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Trang Nguyen Hoa Saif Ullah Munshi Khanh Nguyen Ngoc Chau Le Ngoc Thanh Tran Thi Thanh Tahmina Akther Shahina Tabassum Nilufa Parvin Stephen Baker Motiur Rahman A tightly clustered hepatitis E virus genotype 1a is associated with endemic and outbreak infections in Bangladesh.
description	<h4>Background</h4>Hepatitis E virus (HEV) infection is endemic in Bangladesh and there are occasional outbreaks. The molecular characteristics and pathogenesis of endemic and outbreak HEV strains are poorly understood. We compared the genetic relatedness and virulence associated mutations of endemic HEV strains with outbreak strains.<h4>Methods</h4>We analyzed systematically collected serum samples from HEV immunoglobulin M (IgM) positive patients attended at Bangabandhu Sheikh Mujib Medical University, Dhaka from August 2013 to June 2015. HEV RNA positive samples were subjected to whole genome sequencing. Genotype and subtype of the strains were determined by phylogenetic analysis. Virulence associated mutations e.g. acute viral hepatitis (AVH), fulminant hepatic failure (FHF), chronic hepatitis, ribavirin treatment failure (RTF), B and T cell neutralization epitopes were determined.<h4>Results</h4>92 HEV immunoglobulin M (IgM) antibody positive plasma samples (43 in 2013-2014 and 49 in 2014-2015) were studied. 77.1% (70/92) of the samples were HEV RNA positive. A 279 bp open reading frame (ORF) 2 and ORF 3 sequence was obtained from 54.2% (38/70) of the strains. Of these 38 strains, whole genome sequence (WGS) was obtained from 21 strains. In phylogenetic analysis of 38 (279 bp) sequence all HEV sequences belonged to genotype 1 and subtype 1a. Further phylogenetic analysis of 21 HEV WGS, Bangladeshi HEV sequences clustered with genotype 1a sequences from neighboring countries. Within genotype 1a cluster, Bangladesh HEV strains formed a separate cluster with the 2010 HEV outbreak strains from northern Bangladesh. 80.9 to 100% of the strains had A317T, T735I, L1120I, L1110F, P259S, V1479I, G1634K mutations associates AVH, FHF and RTF. Mutations in T cell recognition epitope T3, T5, T7 was observed in 76.1%, 100% and 100% of the strains respectively.<h4>Conclusion</h4>Strains of HEV genotype 1a are dominant in Bangladesh and are associated with endemic and outbreak of HEV infection. HEV isolates in Bangladesh have high prevalence of virulence associated mutations and mutation which alters antigenicity to B and T cell epitopes.
format	article
author	Trang Nguyen Hoa Saif Ullah Munshi Khanh Nguyen Ngoc Chau Le Ngoc Thanh Tran Thi Thanh Tahmina Akther Shahina Tabassum Nilufa Parvin Stephen Baker Motiur Rahman
author_facet	Trang Nguyen Hoa Saif Ullah Munshi Khanh Nguyen Ngoc Chau Le Ngoc Thanh Tran Thi Thanh Tahmina Akther Shahina Tabassum Nilufa Parvin Stephen Baker Motiur Rahman
author_sort	Trang Nguyen Hoa
title	A tightly clustered hepatitis E virus genotype 1a is associated with endemic and outbreak infections in Bangladesh.
title_short	A tightly clustered hepatitis E virus genotype 1a is associated with endemic and outbreak infections in Bangladesh.
title_full	A tightly clustered hepatitis E virus genotype 1a is associated with endemic and outbreak infections in Bangladesh.
title_fullStr	A tightly clustered hepatitis E virus genotype 1a is associated with endemic and outbreak infections in Bangladesh.
title_full_unstemmed	A tightly clustered hepatitis E virus genotype 1a is associated with endemic and outbreak infections in Bangladesh.
title_sort	tightly clustered hepatitis e virus genotype 1a is associated with endemic and outbreak infections in bangladesh.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/4dfe8860760448f2a643367073631555
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A tightly clustered hepatitis E virus genotype 1a is associated with endemic and outbreak infections in Bangladesh.

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