Research ExplorerPublicationsHuman liver chimeric mice as a new model of chronic hepatiti...

Human liver chimeric mice as a new model of chronic hepatitis E virus infection and preclinical drug evaluation

Standard

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, Vol. 64, No. 5, 01.05.2016, p. 1033-1040.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Allweiss, L, Gass, S, Giersch, K, Groth, A, Kah, J, Volz, T, Rapp , G, Schöbel, A, Lohse, AW, Polywka, S, Pischke, S, Herker, E, Dandri-Petersen, M & Lütgehetmann, M 2016, 'Human liver chimeric mice as a new model of chronic hepatitis E virus infection and preclinical drug evaluation', J HEPATOL, vol. 64, no. 5, pp. 1033-1040. https://doi.org/10.1016/j.jhep.2016.01.011

APA

Allweiss, L., Gass, S., Giersch, K., Groth, A., Kah, J., Volz, T., Rapp , G., Schöbel, A., Lohse, A. W., Polywka, S., Pischke, S., Herker, E., Dandri-Petersen, M., & Lütgehetmann, M. (2016). Human liver chimeric mice as a new model of chronic hepatitis E virus infection and preclinical drug evaluation. J HEPATOL, 64(5), 1033-1040. https://doi.org/10.1016/j.jhep.2016.01.011

Vancouver

Allweiss L, Gass S, Giersch K, Groth A, Kah J, Volz T et al. Human liver chimeric mice as a new model of chronic hepatitis E virus infection and preclinical drug evaluation. J HEPATOL. 2016 May 1;64(5):1033-1040. https://doi.org/10.1016/j.jhep.2016.01.011

Bibtex

@article{9870f2b5a4d346bf9bc5ca8d5009f2ad,
title = "Human liver chimeric mice as a new model of chronic hepatitis E virus infection and preclinical drug evaluation",
abstract = "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.",
author = "Lena Allweiss and Sofia Gass and Katja Giersch and Anne Groth and Janine Kah and Tassilo Volz and Gianna Rapp and Anja Sch{\"o}bel and Lohse, {Ansgar W} and Susanne Polywka and Sven Pischke and Eva Herker and Maura Dandri-Petersen and Marc L{\"u}tgehetmann",
note = "Copyright {\textcopyright} 2016. Published by Elsevier B.V.",
year = "2016",
month = may,
day = "1",
doi = "10.1016/j.jhep.2016.01.011",
language = "English",
volume = "64",
pages = "1033--1040",
journal = "J HEPATOL",
issn = "0168-8278",
publisher = "Elsevier",
number = "5",

}

RIS

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 -