Human liver chimeric mice as a new model of chronic hepatitis E virus infection and preclinical drug evaluation
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Human liver chimeric mice as a new model of chronic hepatitis E virus infection and preclinical drug evaluation. / Allweiss, Lena; Gass, Sofia ; Giersch, Katja; Groth, Anne; Kah, Janine; Volz, Tassilo; Rapp , Gianna ; Schöbel, Anja; Lohse, Ansgar W; Polywka, Susanne; Pischke, Sven; Herker, Eva; Dandri-Petersen, Maura; Lütgehetmann, Marc.
in: J HEPATOL, Jahrgang 64, Nr. 5, 01.05.2016, S. 1033-1040.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Human liver chimeric mice as a new model of chronic hepatitis E virus infection and preclinical drug evaluation
AU - Allweiss, Lena
AU - Gass, Sofia
AU - Giersch, Katja
AU - Groth, Anne
AU - Kah, Janine
AU - Volz, Tassilo
AU - Rapp , Gianna
AU - Schöbel, Anja
AU - Lohse, Ansgar W
AU - Polywka, Susanne
AU - Pischke, Sven
AU - Herker, Eva
AU - Dandri-Petersen, Maura
AU - Lütgehetmann, Marc
N1 - Copyright © 2016. Published by Elsevier B.V.
PY - 2016/5/1
Y1 - 2016/5/1
N2 - BACKGROUND & AIMS: Hepatitis E virus (HEV) is a major cause of acute hepatitis as well as chronic infection in immunocompromised individuals; however, in vivo infection models are limited. The aim of this study was to establish a small animal model to improve our understanding of HEV replication mechanisms and permit the development of effective therapeutics.METHODS: UPA/SCID/beige mice repopulated with primary human hepatocytes were used for infection experiments with HEV genotype (GT) 1 and 3. Virological parameters were determined at the serological and intrahepatic level by real time PCR, immunohistochemistry and RNA in situ hybridization.RESULTS: Establishment of HEV infection was achieved after intravenous injection of stool-derived virions and following co-housing with HEV-infected animals but not via inoculation of serum-derived HEV. GT 1 infection resulted in a rapid rise of viremia and high stable titres in serum, liver, bile and faeces of infected mice for more than 25 weeks. In contrast, viremia in GT 3 infected mice developed more slowly and displayed lower titres in all analysed tissues as compared to GT 1. HEV-infected human hepatocytes could be visualized using HEV ORF2 and ORF3 specific antibodies and HEV RNA in situ hybridization probes. Finally, six-week administration of ribavirin led to a strong reduction of viral replication in the serum and liver of GT 1 infected mice.CONCLUSION: We established an efficient model of HEV infection to test the efficacy of antiviral agents and to exploit mechanisms of HEV replication and interaction with human hepatocytes in vivo.
AB - BACKGROUND & AIMS: Hepatitis E virus (HEV) is a major cause of acute hepatitis as well as chronic infection in immunocompromised individuals; however, in vivo infection models are limited. The aim of this study was to establish a small animal model to improve our understanding of HEV replication mechanisms and permit the development of effective therapeutics.METHODS: UPA/SCID/beige mice repopulated with primary human hepatocytes were used for infection experiments with HEV genotype (GT) 1 and 3. Virological parameters were determined at the serological and intrahepatic level by real time PCR, immunohistochemistry and RNA in situ hybridization.RESULTS: Establishment of HEV infection was achieved after intravenous injection of stool-derived virions and following co-housing with HEV-infected animals but not via inoculation of serum-derived HEV. GT 1 infection resulted in a rapid rise of viremia and high stable titres in serum, liver, bile and faeces of infected mice for more than 25 weeks. In contrast, viremia in GT 3 infected mice developed more slowly and displayed lower titres in all analysed tissues as compared to GT 1. HEV-infected human hepatocytes could be visualized using HEV ORF2 and ORF3 specific antibodies and HEV RNA in situ hybridization probes. Finally, six-week administration of ribavirin led to a strong reduction of viral replication in the serum and liver of GT 1 infected mice.CONCLUSION: We established an efficient model of HEV infection to test the efficacy of antiviral agents and to exploit mechanisms of HEV replication and interaction with human hepatocytes in vivo.
U2 - 10.1016/j.jhep.2016.01.011
DO - 10.1016/j.jhep.2016.01.011
M3 - SCORING: Journal article
VL - 64
SP - 1033
EP - 1040
JO - J HEPATOL
JF - J HEPATOL
SN - 0168-8278
IS - 5
ER -