A tightly clustered hepatitis E virus genotype 1a is associated with endemic and outbreak infections in Bangladesh
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...
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creator | Hoa, Trang Nguyen Munshi, Saif Ullah Ngoc, Khanh Nguyen Ngoc, Chau Le Thanh, Thanh Tran Thi Akther, Tahmina Tabassum, Shahina Parvin, Nilufa Baker, Stephen Rahman, Motiur |
description | 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. 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. 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. 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. |
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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. 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. 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. 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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0255054</identifier><identifier>PMID: 34293039</identifier><language>eng</language><publisher>San Francisco: Public Library of Science</publisher><subject>Analysis ; Antibodies ; Antigenicity ; Biology and life sciences ; Cell recognition ; Clusters ; Computer and Information Sciences ; Disease ; Epidemics ; Epitopes ; Food contamination & poisoning ; Gene sequencing ; Genetic aspects ; Genomes ; Genotype & phenotype ; Genotypes ; Hepatitis ; Hepatitis E virus ; Hospitals ; Immunoglobulin M ; Infections ; Lymphocytes ; Lymphocytes T ; Medicine and health sciences ; Mutation ; Neutralization ; Nucleotide sequence ; Open reading frames ; Outbreaks ; Pathogenesis ; Patients ; People and Places ; Phylogenetics ; Phylogeny ; Proteins ; Research and analysis methods ; Ribavirin ; Ribonucleic acid ; RNA ; Strains (organisms) ; Tropical diseases ; Virulence ; Virulence (Microbiology) ; Viruses ; Whole genome sequencing</subject><ispartof>PloS one, 2021-07, Vol.16 (7), p.e0255054-e0255054</ispartof><rights>COPYRIGHT 2021 Public Library of Science</rights><rights>2021 Hoa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 Hoa et al 2021 Hoa et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c669t-c00eef1f83a2ba1cd112d6cd1fd4c9e9d8710f0bd2540c1f8fb3cd6a7d69ffba3</citedby><cites>FETCH-LOGICAL-c669t-c00eef1f83a2ba1cd112d6cd1fd4c9e9d8710f0bd2540c1f8fb3cd6a7d69ffba3</cites><orcidid>0000-0002-6702-5355 ; 0000-0002-8568-5875</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8297744/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8297744/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,861,882,2096,2915,23847,27905,27906,53772,53774,79349,79350</link.rule.ids></links><search><contributor>Roques, Pierre</contributor><creatorcontrib>Hoa, Trang Nguyen</creatorcontrib><creatorcontrib>Munshi, Saif Ullah</creatorcontrib><creatorcontrib>Ngoc, Khanh Nguyen</creatorcontrib><creatorcontrib>Ngoc, Chau Le</creatorcontrib><creatorcontrib>Thanh, Thanh Tran Thi</creatorcontrib><creatorcontrib>Akther, Tahmina</creatorcontrib><creatorcontrib>Tabassum, Shahina</creatorcontrib><creatorcontrib>Parvin, Nilufa</creatorcontrib><creatorcontrib>Baker, Stephen</creatorcontrib><creatorcontrib>Rahman, Motiur</creatorcontrib><title>A tightly clustered hepatitis E virus genotype 1a is associated with endemic and outbreak infections in Bangladesh</title><title>PloS one</title><description>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. 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. 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. 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.</description><subject>Analysis</subject><subject>Antibodies</subject><subject>Antigenicity</subject><subject>Biology and life sciences</subject><subject>Cell recognition</subject><subject>Clusters</subject><subject>Computer and Information Sciences</subject><subject>Disease</subject><subject>Epidemics</subject><subject>Epitopes</subject><subject>Food contamination & poisoning</subject><subject>Gene sequencing</subject><subject>Genetic aspects</subject><subject>Genomes</subject><subject>Genotype & phenotype</subject><subject>Genotypes</subject><subject>Hepatitis</subject><subject>Hepatitis E virus</subject><subject>Hospitals</subject><subject>Immunoglobulin M</subject><subject>Infections</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Medicine and health sciences</subject><subject>Mutation</subject><subject>Neutralization</subject><subject>Nucleotide sequence</subject><subject>Open reading frames</subject><subject>Outbreaks</subject><subject>Pathogenesis</subject><subject>Patients</subject><subject>People and Places</subject><subject>Phylogenetics</subject><subject>Phylogeny</subject><subject>Proteins</subject><subject>Research and analysis methods</subject><subject>Ribavirin</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>Strains (organisms)</subject><subject>Tropical diseases</subject><subject>Virulence</subject><subject>Virulence (Microbiology)</subject><subject>Viruses</subject><subject>Whole genome 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tightly clustered hepatitis E virus genotype 1a is associated with endemic and outbreak infections in Bangladesh</title><author>Hoa, Trang Nguyen ; Munshi, Saif Ullah ; Ngoc, Khanh Nguyen ; Ngoc, Chau Le ; Thanh, Thanh Tran Thi ; Akther, Tahmina ; Tabassum, Shahina ; Parvin, Nilufa ; Baker, Stephen ; Rahman, Motiur</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c669t-c00eef1f83a2ba1cd112d6cd1fd4c9e9d8710f0bd2540c1f8fb3cd6a7d69ffba3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Analysis</topic><topic>Antibodies</topic><topic>Antigenicity</topic><topic>Biology and life sciences</topic><topic>Cell recognition</topic><topic>Clusters</topic><topic>Computer and Information Sciences</topic><topic>Disease</topic><topic>Epidemics</topic><topic>Epitopes</topic><topic>Food contamination & poisoning</topic><topic>Gene sequencing</topic><topic>Genetic 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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. 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. 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. 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.</abstract><cop>San Francisco</cop><pub>Public Library of Science</pub><pmid>34293039</pmid><doi>10.1371/journal.pone.0255054</doi><tpages>e0255054</tpages><orcidid>https://orcid.org/0000-0002-6702-5355</orcidid><orcidid>https://orcid.org/0000-0002-8568-5875</orcidid><oa>free_for_read</oa></addata></record> |
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identifier | ISSN: 1932-6203 |
ispartof | PloS one, 2021-07, Vol.16 (7), p.e0255054-e0255054 |
issn | 1932-6203 1932-6203 |
language | eng |
recordid | cdi_gale_infotracacademiconefile_A669333895 |
source | DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
subjects | Analysis Antibodies Antigenicity Biology and life sciences Cell recognition Clusters Computer and Information Sciences Disease Epidemics Epitopes Food contamination & poisoning Gene sequencing Genetic aspects Genomes Genotype & phenotype Genotypes Hepatitis Hepatitis E virus Hospitals Immunoglobulin M Infections Lymphocytes Lymphocytes T Medicine and health sciences Mutation Neutralization Nucleotide sequence Open reading frames Outbreaks Pathogenesis Patients People and Places Phylogenetics Phylogeny Proteins Research and analysis methods Ribavirin Ribonucleic acid RNA Strains (organisms) Tropical diseases Virulence Virulence (Microbiology) Viruses Whole genome sequencing |
title | A tightly clustered hepatitis E virus genotype 1a is associated with endemic and outbreak infections in Bangladesh |
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