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High sensitivity of domestic pigs to intravenous infection with HEV

BACKGROUND: Hepatitis E virus (HEV) is one major cause of acute clinical hepatitis among humans throughout the world. In industrialized countries an increasing number of autochthonous HEV infections have been identified over the last years triggered by food borne as well as – to a much lower degree...

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Autores principales: Dähnert, Lisa, Eiden, Martin, Schlosser, Josephine, Fast, Christine, Schröder, Charlotte, Lange, Elke, Gröner, Albrecht, Schäfer, Wolfram, Groschup, Martin H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6278151/
https://www.ncbi.nlm.nih.gov/pubmed/30514313
http://dx.doi.org/10.1186/s12917-018-1713-8
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author Dähnert, Lisa
Eiden, Martin
Schlosser, Josephine
Fast, Christine
Schröder, Charlotte
Lange, Elke
Gröner, Albrecht
Schäfer, Wolfram
Groschup, Martin H.
author_facet Dähnert, Lisa
Eiden, Martin
Schlosser, Josephine
Fast, Christine
Schröder, Charlotte
Lange, Elke
Gröner, Albrecht
Schäfer, Wolfram
Groschup, Martin H.
author_sort Dähnert, Lisa
collection PubMed
description BACKGROUND: Hepatitis E virus (HEV) is one major cause of acute clinical hepatitis among humans throughout the world. In industrialized countries an increasing number of autochthonous HEV infections have been identified over the last years triggered by food borne as well as – to a much lower degree – by human to human transmission via blood transfusion. Pigs have been recognised as main reservoir for HEV genotype 3 (HEV-3), and zoonotic transmission to humans through undercooked/raw meat is reported repeatedly. The minimal infectious dose of HEV-3 for pigs is so far unknown. RESULTS: The minimum infectious dose of HEV-3 in a pig infection model was determined by intravenous inoculation of pigs with a dilution series of a liver homogenate of a HEV infected wild boar. Seroconversion, virus replication and shedding were determined by analysis of blood and faeces samples, collected over a maximum period of 91 days. A dose dependent incubation period was observed in faecal shedding of viruses employing a specific and sensitive PCR method. Faecal viral shedding and seroconversion was detected in animals inoculated with dilutions of up to 10(− 7). This correlates with an intravenously (i.v.) administered infectious dose of only 6.5 copies in 2 ml (corresponding to 24 IU HEV RNA/ml). Furthermore the first detectable shedding of HEV RNA in faeces is clearly dose dependent. Unexpectedly one group infected with a 10(− 4) dilution exhibited prolonged virus shedding for more than 60 days suggesting a persistent infection. CONCLUSION: The results indicate that pigs are highly susceptible to i.v. infection with HEV and that the swine model represents the most sensitive infectivity assay for HEV so far. Considering a minimum infectious dose of 24 IU RNA/ml our findings highlights the potential risk of HEV transmission via blood and blood products. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12917-018-1713-8) contains supplementary material, which is available to authorized users.
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spelling pubmed-62781512018-12-10 High sensitivity of domestic pigs to intravenous infection with HEV Dähnert, Lisa Eiden, Martin Schlosser, Josephine Fast, Christine Schröder, Charlotte Lange, Elke Gröner, Albrecht Schäfer, Wolfram Groschup, Martin H. BMC Vet Res Research Article BACKGROUND: Hepatitis E virus (HEV) is one major cause of acute clinical hepatitis among humans throughout the world. In industrialized countries an increasing number of autochthonous HEV infections have been identified over the last years triggered by food borne as well as – to a much lower degree – by human to human transmission via blood transfusion. Pigs have been recognised as main reservoir for HEV genotype 3 (HEV-3), and zoonotic transmission to humans through undercooked/raw meat is reported repeatedly. The minimal infectious dose of HEV-3 for pigs is so far unknown. RESULTS: The minimum infectious dose of HEV-3 in a pig infection model was determined by intravenous inoculation of pigs with a dilution series of a liver homogenate of a HEV infected wild boar. Seroconversion, virus replication and shedding were determined by analysis of blood and faeces samples, collected over a maximum period of 91 days. A dose dependent incubation period was observed in faecal shedding of viruses employing a specific and sensitive PCR method. Faecal viral shedding and seroconversion was detected in animals inoculated with dilutions of up to 10(− 7). This correlates with an intravenously (i.v.) administered infectious dose of only 6.5 copies in 2 ml (corresponding to 24 IU HEV RNA/ml). Furthermore the first detectable shedding of HEV RNA in faeces is clearly dose dependent. Unexpectedly one group infected with a 10(− 4) dilution exhibited prolonged virus shedding for more than 60 days suggesting a persistent infection. CONCLUSION: The results indicate that pigs are highly susceptible to i.v. infection with HEV and that the swine model represents the most sensitive infectivity assay for HEV so far. Considering a minimum infectious dose of 24 IU RNA/ml our findings highlights the potential risk of HEV transmission via blood and blood products. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12917-018-1713-8) contains supplementary material, which is available to authorized users. BioMed Central 2018-12-04 /pmc/articles/PMC6278151/ /pubmed/30514313 http://dx.doi.org/10.1186/s12917-018-1713-8 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Dähnert, Lisa
Eiden, Martin
Schlosser, Josephine
Fast, Christine
Schröder, Charlotte
Lange, Elke
Gröner, Albrecht
Schäfer, Wolfram
Groschup, Martin H.
High sensitivity of domestic pigs to intravenous infection with HEV
title High sensitivity of domestic pigs to intravenous infection with HEV
title_full High sensitivity of domestic pigs to intravenous infection with HEV
title_fullStr High sensitivity of domestic pigs to intravenous infection with HEV
title_full_unstemmed High sensitivity of domestic pigs to intravenous infection with HEV
title_short High sensitivity of domestic pigs to intravenous infection with HEV
title_sort high sensitivity of domestic pigs to intravenous infection with hev
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6278151/
https://www.ncbi.nlm.nih.gov/pubmed/30514313
http://dx.doi.org/10.1186/s12917-018-1713-8
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