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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Veröffentlicht in:PloS one 2021-07, Vol.16 (7), p.e0255054-e0255054
Hauptverfasser: 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
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container_volume 16
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.
doi_str_mv 10.1371/journal.pone.0255054
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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. 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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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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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