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Hepatitis E virus genotypes and subgenotypes causing acute hepatitis, Bulgaria, 2013–2015

BACKGROUND: In industrialized areas of the world, including Europe, Hepatitis E Virus (HEV) is considered an emerging pathogen. In fact, autochthonous cases caused by HEV genotype 3 (HEV-3) are increasingly reported. Several studies described the human HEV-3 subtypes and strains circulating in West...

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Autores principales: Bruni, Roberto, Villano, Umbertina, Equestre, Michele, Chionne, Paola, Madonna, Elisabetta, Trandeva-Bankova, Dilyana, Peleva-Pishmisheva, Maria, Tenev, Tencho, Cella, Eleonora, Ciccozzi, Massimo, Pisani, Giulio, Golkocheva-Markova, Elitsa, Ciccaglione, Anna Rita
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5991722/
https://www.ncbi.nlm.nih.gov/pubmed/29879148
http://dx.doi.org/10.1371/journal.pone.0198045
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author Bruni, Roberto
Villano, Umbertina
Equestre, Michele
Chionne, Paola
Madonna, Elisabetta
Trandeva-Bankova, Dilyana
Peleva-Pishmisheva, Maria
Tenev, Tencho
Cella, Eleonora
Ciccozzi, Massimo
Pisani, Giulio
Golkocheva-Markova, Elitsa
Ciccaglione, Anna Rita
author_facet Bruni, Roberto
Villano, Umbertina
Equestre, Michele
Chionne, Paola
Madonna, Elisabetta
Trandeva-Bankova, Dilyana
Peleva-Pishmisheva, Maria
Tenev, Tencho
Cella, Eleonora
Ciccozzi, Massimo
Pisani, Giulio
Golkocheva-Markova, Elitsa
Ciccaglione, Anna Rita
author_sort Bruni, Roberto
collection PubMed
description BACKGROUND: In industrialized areas of the world, including Europe, Hepatitis E Virus (HEV) is considered an emerging pathogen. In fact, autochthonous cases caused by HEV genotype 3 (HEV-3) are increasingly reported. Several studies described the human HEV-3 subtypes and strains circulating in West Europe countries; in contrast, very little is known about the HEV strains responsible for acute hepatitis E in countries of East Europe/Balkans, such as Bulgaria. METHODS AND FINDINGS: Anti-HEV IgM positive serum samples (n = 103) from acute hepatitis cases (2013–2015) from all over Bulgaria were analysed for HEV RNA by Real-Time PCR. Viremia was detected in 90/103 samples. A fragment of the viral genome (ORF-2 region) was amplified by nested PCR from 76/90 viremic samples, leading to a sequence in 64 of them. Genotyping by phylogenetic analysis with standard reference sequences showed HEV-1 in 1/64 cases, HEV-3 in 63/64. Subtyping of HEV-3 sequences showed 3e (39/63, 62%), 3f (n = 15/63, 24%) and 3c (n = 8/63, 13%) subtypes; in one case the sequence subtype was uncertain and classified as 3hi. In the phylogenetic tree, most 3e sequences grouped in two well distinct clusters (A and B), each one with very low intragroup genetic distances. In contrast, 3f and 3c were interspersed with reference sequences and showed lower tendency to cluster and/or higher intragroup distances. Geographically, while 3f and 3c were scattered throughout the country, 3e was restricted to the South-West area, with most cases in two towns about 40 kilometres apart from each other. CONCLUSIONS: Most acute hepatitis E cases in Bulgaria are caused by HEV-3, subtypes 3e, 3f and 3c. Circulation of 3e appears quite different from 3f and 3c, with 3e restricted to the South-West area while 3f and 3c diffused over the country. The factors underlying the observed molecular and geographical differences remain to be investigated.
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spelling pubmed-59917222018-06-16 Hepatitis E virus genotypes and subgenotypes causing acute hepatitis, Bulgaria, 2013–2015 Bruni, Roberto Villano, Umbertina Equestre, Michele Chionne, Paola Madonna, Elisabetta Trandeva-Bankova, Dilyana Peleva-Pishmisheva, Maria Tenev, Tencho Cella, Eleonora Ciccozzi, Massimo Pisani, Giulio Golkocheva-Markova, Elitsa Ciccaglione, Anna Rita PLoS One Research Article BACKGROUND: In industrialized areas of the world, including Europe, Hepatitis E Virus (HEV) is considered an emerging pathogen. In fact, autochthonous cases caused by HEV genotype 3 (HEV-3) are increasingly reported. Several studies described the human HEV-3 subtypes and strains circulating in West Europe countries; in contrast, very little is known about the HEV strains responsible for acute hepatitis E in countries of East Europe/Balkans, such as Bulgaria. METHODS AND FINDINGS: Anti-HEV IgM positive serum samples (n = 103) from acute hepatitis cases (2013–2015) from all over Bulgaria were analysed for HEV RNA by Real-Time PCR. Viremia was detected in 90/103 samples. A fragment of the viral genome (ORF-2 region) was amplified by nested PCR from 76/90 viremic samples, leading to a sequence in 64 of them. Genotyping by phylogenetic analysis with standard reference sequences showed HEV-1 in 1/64 cases, HEV-3 in 63/64. Subtyping of HEV-3 sequences showed 3e (39/63, 62%), 3f (n = 15/63, 24%) and 3c (n = 8/63, 13%) subtypes; in one case the sequence subtype was uncertain and classified as 3hi. In the phylogenetic tree, most 3e sequences grouped in two well distinct clusters (A and B), each one with very low intragroup genetic distances. In contrast, 3f and 3c were interspersed with reference sequences and showed lower tendency to cluster and/or higher intragroup distances. Geographically, while 3f and 3c were scattered throughout the country, 3e was restricted to the South-West area, with most cases in two towns about 40 kilometres apart from each other. CONCLUSIONS: Most acute hepatitis E cases in Bulgaria are caused by HEV-3, subtypes 3e, 3f and 3c. Circulation of 3e appears quite different from 3f and 3c, with 3e restricted to the South-West area while 3f and 3c diffused over the country. The factors underlying the observed molecular and geographical differences remain to be investigated. Public Library of Science 2018-06-07 /pmc/articles/PMC5991722/ /pubmed/29879148 http://dx.doi.org/10.1371/journal.pone.0198045 Text en © 2018 Bruni et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Bruni, Roberto
Villano, Umbertina
Equestre, Michele
Chionne, Paola
Madonna, Elisabetta
Trandeva-Bankova, Dilyana
Peleva-Pishmisheva, Maria
Tenev, Tencho
Cella, Eleonora
Ciccozzi, Massimo
Pisani, Giulio
Golkocheva-Markova, Elitsa
Ciccaglione, Anna Rita
Hepatitis E virus genotypes and subgenotypes causing acute hepatitis, Bulgaria, 2013–2015
title Hepatitis E virus genotypes and subgenotypes causing acute hepatitis, Bulgaria, 2013–2015
title_full Hepatitis E virus genotypes and subgenotypes causing acute hepatitis, Bulgaria, 2013–2015
title_fullStr Hepatitis E virus genotypes and subgenotypes causing acute hepatitis, Bulgaria, 2013–2015
title_full_unstemmed Hepatitis E virus genotypes and subgenotypes causing acute hepatitis, Bulgaria, 2013–2015
title_short Hepatitis E virus genotypes and subgenotypes causing acute hepatitis, Bulgaria, 2013–2015
title_sort hepatitis e virus genotypes and subgenotypes causing acute hepatitis, bulgaria, 2013–2015
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5991722/
https://www.ncbi.nlm.nih.gov/pubmed/29879148
http://dx.doi.org/10.1371/journal.pone.0198045
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