High sensitivity of domestic pigs to intravenous infection with HEV

Abstract 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...

Full description

Bibliographic Details
Main Authors: Lisa Dähnert, Martin Eiden, Josephine Schlosser, Christine Fast, Charlotte Schröder, Elke Lange, Albrecht Gröner, Wolfram Schäfer, Martin H. Groschup
Format: Article
Language:English
Published: BMC 2018-12-01
Series:BMC Veterinary Research
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12917-018-1713-8
_version_ 1818673186130100224
author Lisa Dähnert
Martin Eiden
Josephine Schlosser
Christine Fast
Charlotte Schröder
Elke Lange
Albrecht Gröner
Wolfram Schäfer
Martin H. Groschup
author_facet Lisa Dähnert
Martin Eiden
Josephine Schlosser
Christine Fast
Charlotte Schröder
Elke Lange
Albrecht Gröner
Wolfram Schäfer
Martin H. Groschup
author_sort Lisa Dähnert
collection DOAJ
description Abstract 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.
first_indexed 2024-12-17T07:51:47Z
format Article
id doaj.art-9897f6b410fd4d858c44ac0e0b109b06
institution Directory Open Access Journal
issn 1746-6148
language English
last_indexed 2024-12-17T07:51:47Z
publishDate 2018-12-01
publisher BMC
record_format Article
series BMC Veterinary Research
spelling doaj.art-9897f6b410fd4d858c44ac0e0b109b062022-12-21T21:57:49ZengBMCBMC Veterinary Research1746-61482018-12-0114111210.1186/s12917-018-1713-8High sensitivity of domestic pigs to intravenous infection with HEVLisa Dähnert0Martin Eiden1Josephine Schlosser2Christine Fast3Charlotte Schröder4Elke Lange5Albrecht Gröner6Wolfram Schäfer7Martin H. Groschup8Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-InstitutInstitute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-InstitutDepartment of Veterinary Medicine, Institute of Immunology, Freie Universität BerlinInstitute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-InstitutDepartment of Experimental Animal Facilities and Biorisk Management, Friedrich-Loeffler-InstitutDepartment of Experimental Animal Facilities and Biorisk Management, Friedrich-Loeffler-InstitutPathoGuard ConsultCSL Behring Biotherapies for Life™Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-InstitutAbstract 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.http://link.springer.com/article/10.1186/s12917-018-1713-8HEVMinimal infectious doseSwineIn vivo
spellingShingle Lisa Dähnert
Martin Eiden
Josephine Schlosser
Christine Fast
Charlotte Schröder
Elke Lange
Albrecht Gröner
Wolfram Schäfer
Martin H. Groschup
High sensitivity of domestic pigs to intravenous infection with HEV
BMC Veterinary Research
HEV
Minimal infectious dose
Swine
In vivo
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 HEV
Minimal infectious dose
Swine
In vivo
url http://link.springer.com/article/10.1186/s12917-018-1713-8
work_keys_str_mv AT lisadahnert highsensitivityofdomesticpigstointravenousinfectionwithhev
AT martineiden highsensitivityofdomesticpigstointravenousinfectionwithhev
AT josephineschlosser highsensitivityofdomesticpigstointravenousinfectionwithhev
AT christinefast highsensitivityofdomesticpigstointravenousinfectionwithhev
AT charlotteschroder highsensitivityofdomesticpigstointravenousinfectionwithhev
AT elkelange highsensitivityofdomesticpigstointravenousinfectionwithhev
AT albrechtgroner highsensitivityofdomesticpigstointravenousinfectionwithhev
AT wolframschafer highsensitivityofdomesticpigstointravenousinfectionwithhev
AT martinhgroschup highsensitivityofdomesticpigstointravenousinfectionwithhev