Hepatitis E virus genotype 3 microbiological surveillance by the Spanish Reference Laboratory: geographic distribution and phylogenetic analysis of subtypes from 2009 to 2019

Muñoz-Chimeno, Milagros; Bartúren, Silvia; García-Lugo, Maira Alejandra; Morago, Lucia; Rodríguez, Álvaro; Galán, Juan Carlos; Pérez‐Rivilla, Alfredo; Rodríguez, Mercedes; Millán, Rosario San; Álamo, Manuel del; Alonso, Roberto; Molina, Laura; Aguinaga, Aitziber; Avellón, Ana

doi:10.2807/1560-7917.es.2022.27.23.2100542

Cited by 17 publications

(21 citation statements)

References 31 publications

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“…Sequence collection for genome analysis and sub-genotype assignment HEV-3 genomes included in the analysis were retrieved from GenBank, 74 of which had previously been obtained in our laboratory (MZ289076-MZ289149; Munoz-Chimeno et al, 2022) and 439 were additional complete genomes retrieved from GenBank database in October 2021 (detailed in Supplementary material). In addition, 60 HEV-1 and 92 HEV-4 sequences from GenBank were used for entropy analysis (see Supplementary material).…”

Section: Methodsmentioning

confidence: 99%

“…In addition, 60 HEV-1 and 92 HEV-4 sequences from GenBank were used for entropy analysis (see Supplementary material ). Reference sequences proposed by Smith et al (2020) and Munoz-Chimeno et al (2022) were used.…”

Section: Methodsmentioning

confidence: 99%

“…Sub-genotypes were checked by phylogenetic analysis as described elsewhere ( Munoz-Chimeno et al, 2022 ).…”

Section: Methodsmentioning

confidence: 99%

“…HEV genotype 3 (HEV-3) is a zoonosis. Pigs are its most important reservoir and it is transmitted through the consumption of raw or undercooked meat (Garcia et al, 2019). According to Smith et al (2020), HEV-3 is further divided into subtypes 3a, 3b, 3c, 3e, 3f, 3g, 3h, 3i, 3j, 3k, 3l, 3m and some unassigned sequences.…”

Section: Introductionmentioning

confidence: 99%

“…The latter clade is further divided into HEV-3abjk and HEV-3chilm. A recent study divided HEV-3f into three clusters (HEV-3f-A1, HEV-3f-A2 and HEV-3f-B), and HEV-3m into HEV-3m-A and HEV-3m-B, based on p-distance and phylogenetic analysis ( Munoz-Chimeno et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

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Hepatitis E genotype 3 genome: A comprehensive analysis of entropy, motif conservation, relevant mutations, and clade-associated polymorphisms

et al. 2022

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Hepatitis E virus genotype 3 (HEV-3) is an EU/EEA emergent zoonosis. HEV-3 clades/subtypes have been described. Its genome contains ORF1, which encodes nonstructural proteins for virus replication, ORF2, the capsid protein, and ORF3, a multifunctional protein involved in virion pathogenesis. The study aims with respect to HEV-3 are to: (1) calculate genome entropy (excluding hypervariable region); (2) analyze the described motifs/mutations; (3) characterize clade/subtype genome polymorphisms. Seven hundred and five sequences from the GenBank database were used. The highest entropies were identified in zoonotic genotypes (HEV-3 and HEV-4) with respect to HEV-1 in X domain, RdRp, ORF2, and ORF3. There were statistically significant differences in the entropy between proteins, protease and ORF3 being the most variable and Y domain being the most conserved. Methyltransferase and Y domain motifs were completely conserved. By contrast, essential protease H581 residue and catalytic dyad exhibited amino acid changes in 1.8% and 0.4% of sequences, respectively. Several X domain amino acids were associated with clades. We found sequences with mutations in all helicase motifs except number IV. Helicase mutations related to increased virulence and/or fulminant hepatitis were frequent, the 1,110 residue being a typical HEV-3e and HEV-3f-A2 polymorphism. RdRp motifs III, V, VII also had high mutation rates. Motif III included residues that are polymorphisms of HEV-3e (F1449) and HEV-3 m (D1451). RdRp ribavirin resistance mutations were frequent, mainly 1479I (67.4, 100% in HEV-3efglmk) and 1634R/K (10.0%, almost 100% in HEV-3e). With respect to ORF2, 19/27 neutralization epitopes had mutations. The S80 residue in ORF3 presented mutations in 3.5% of cases. Amino acids in the ORF3-PSAP motif had high substitution rates, being more frequent in the first PSAP (44.8%) than in the second (1.5%). This is the first comprehensive analysis of the HEV-3 genome, aimed at improving our knowledge of the genome, and establishing the basis for future genotype-to-phenotype analysis, given that viral features associated with severity have not been explored in depth. Our results demonstrate there are important genetic differences in the studied genomes that sometimes affect significant viral structures, and constitute clade/subtype polymorphisms that may affect the clinical course or treatment efficacy.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…Sub-genotypes were checked by phylogenetic analysis as described elsewhere ( Munoz-Chimeno et al, 2022 ).…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Hepatitis E genotype 3 genome: A comprehensive analysis of entropy, motif conservation, relevant mutations, and clade-associated polymorphisms

et al. 2022

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Hepatitis E Virus in the Iberian Peninsula: A Systematic Review

et al. 2023

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One of the most frequent causes of acute viral hepatitis is hepatitis E virus (HEV) causing 20 million infections worldwide each year and 44,000 deaths. Studies on HEV in the Iberian Peninsula have been increasing through time with HEV infection being identified in humans and animals. The aim of the present systematic review was to compile and evaluate all the published data on HEV from studies performed in humans, animals and environmental samples in the Iberian Peninsula. The electronic databases Mendeley, PubMed, Scopus, and Web of Science were thoroughly searched, and research published up until February 01, 2023 were included. Resulting in a total of 151 eligible papers by full reading and application of PRISMA exclusion/inclusion criteria. Overall, the present review shows that several HEV genotypes, namely HEV-1, 3, 4, and 6 as well as Rocahepevirus, are circulating in humans, animals, and in the environment in the Iberian Peninsula. HEV-3 was the most common genotype circulating in humans in Portugal and Spain, as expected for developed countries, with HEV-1 only being detected in travelers and emigrants from HEV endemic regions. Spain is the biggest pork producer in Europe and given the high circulation of HEV in pigs, with HEV-3 being primarily associated to zoonotic transmission through consumption of swine meat and meat products, in our opinion, the introduction of an HEV surveillance system in swine and inclusion of HEV in diagnostic routines for acute and chronic human hepatitis would be important. Additionally, we propose that establishing a monitoring mechanism for HEV is crucial in order to gain a comprehensive understanding of the prevalence of this illness and the various strains present in the Iberian Peninsula, as well as their potential impact on public health.

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Metabarcoding of Hepatitis E Virus Genotype 3 and Norovirus GII from Wastewater Samples in England Using Nanopore Sequencing

Treagus,

Lowther,

Longdon

et al. 2023

Food Environ Virol

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Norovirus is one of the largest causes of gastroenteritis worldwide, and Hepatitis E virus (HEV) is an emerging pathogen that has become the most dominant cause of acute viral hepatitis in recent years. The presence of norovirus and HEV has been reported within wastewater in many countries previously. Here we used amplicon deep sequencing (metabarcoding) to identify norovirus and HEV strains in wastewater samples from England collected in 2019 and 2020. For HEV, we sequenced a fragment of the RNA-dependent RNA polymerase (RdRp) gene targeting genotype three strains. For norovirus, we sequenced the 5′ portion of the major capsid protein gene (VP1) of genogroup II strains. Sequencing of the wastewater samples revealed eight different genotypes of norovirus GII (GII.2, GII.3, GII.4, GII.6, GII.7, GII.9, GII.13 and GII.17). Genotypes GII.3 and GII.4 were the most commonly found. The HEV metabarcoding assay was able to identify HEV genotype 3 strains in some samples with a very low viral concentration determined by RT-qPCR. Analysis showed that most HEV strains found in influent wastewater were typed as G3c and G3e and were likely to have originated from humans or swine. However, the small size of the HEV nested PCR amplicon could cause issues with typing, and so this method is more appropriate for samples with high CTs where methods targeting longer genomic regions are unlikely to be successful. This is the first report of HEV RNA in wastewater in England. This study demonstrates the utility of wastewater sequencing and the need for wider surveillance of norovirus and HEV within host species and environments.

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Hepatitis E virus genotype 3 microbiological surveillance by the Spanish Reference Laboratory: geographic distribution and phylogenetic analysis of subtypes from 2009 to 2019

Cited by 17 publications

References 31 publications

Hepatitis E genotype 3 genome: A comprehensive analysis of entropy, motif conservation, relevant mutations, and clade-associated polymorphisms

Hepatitis E genotype 3 genome: A comprehensive analysis of entropy, motif conservation, relevant mutations, and clade-associated polymorphisms

Hepatitis E Virus in the Iberian Peninsula: A Systematic Review

Metabarcoding of Hepatitis E Virus Genotype 3 and Norovirus GII from Wastewater Samples in England Using Nanopore Sequencing

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