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Hepatitis Delta co-infection in humanized mice leads to pronounced induction of innate immune responses in comparison to HBV mono-infection

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Hepatitis Delta co-infection in humanized mice leads to pronounced induction of innate immune responses in comparison to HBV mono-infection. / Giersch, Katja; Allweiss, Lena; Volz, Tassilo; Helbig, Martina; Bierwolf, Jeanette; Lohse, Ansgar W; Pollok, Joerg M; Petersen, Joerg; Dandri-Petersen, Maura; Lütgehetmann, Marc.

In: J HEPATOL, Vol. 63, No. 2, 08.2015, p. 346-53.

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

Harvard

Giersch, K, Allweiss, L, Volz, T, Helbig, M, Bierwolf, J, Lohse, AW, Pollok, JM, Petersen, J, Dandri-Petersen, M & Lütgehetmann, M 2015, 'Hepatitis Delta co-infection in humanized mice leads to pronounced induction of innate immune responses in comparison to HBV mono-infection', J HEPATOL, vol. 63, no. 2, pp. 346-53. https://doi.org/10.1016/j.jhep.2015.03.011

APA

Giersch, K., Allweiss, L., Volz, T., Helbig, M., Bierwolf, J., Lohse, A. W., Pollok, J. M., Petersen, J., Dandri-Petersen, M., & Lütgehetmann, M. (2015). Hepatitis Delta co-infection in humanized mice leads to pronounced induction of innate immune responses in comparison to HBV mono-infection. J HEPATOL, 63(2), 346-53. https://doi.org/10.1016/j.jhep.2015.03.011

Vancouver

Giersch K, Allweiss L, Volz T, Helbig M, Bierwolf J, Lohse AW et al. Hepatitis Delta co-infection in humanized mice leads to pronounced induction of innate immune responses in comparison to HBV mono-infection. J HEPATOL. 2015 Aug;63(2):346-53. https://doi.org/10.1016/j.jhep.2015.03.011

Bibtex

@article{20add7d35247456388fe77b4e177cb1e,
title = "Hepatitis Delta co-infection in humanized mice leads to pronounced induction of innate immune responses in comparison to HBV mono-infection",
abstract = "BACKGROUND & AIMS: The limited availability of hepatitis Delta virus (HDV) infection models has hindered studies of interactions between HDV and infected hepatocytes. The aim was to investigate the antiviral state of HDV infected human hepatocytes in the setting of co-infection with hepatitis B virus (HBV) compared to HBV mono-infection using human liver chimeric mice.METHODS: Viral loads, human interferon stimulated genes (hISGs) and cytokines were determined in humanized uPA/SCID/beige (USB) mice by qRT-PCR, ELISA and immunofluorescence.RESULTS: Upon HBV/HDV inoculation, all mice developed viremia, which was accompanied by a significant induction of hISGs (i.e. hISG15, hSTATs, hHLA-E) compared to uninfected mice, while HBV mono-infection led to weaker hISG elevations. In the setting of chronic infection enhancement of innate defense mechanisms was significantly more prominent in HBV/HDV infected mice. Also the induction of human-specific cytokines (hIP10, hTGF-{\ss}, hIFN-{\ss} and hIFN-λ) was detected in HBV/HDV co-infected animals, while levels remained lower or below detection in uninfected and HBV mono-infected mice. Moreover, despite the average increase of hSTAT levels determined in HBV/HDV infected livers, we observed a weaker hSTAT accumulation in nuclei of hepatocytes displaying very high HDAg levels, suggesting that HDAg may in part limit hSTAT signaling.CONCLUSIONS: Establishment of HDV infection provoked a clear enhancement of the antiviral state of the human hepatocytes in chimeric mice. Elevated pre-treatment ISG and interferon levels may directly contribute to inflammation and liver damage, providing a rationale for the more severe course of HDV-associated liver disease. Such antiviral state induction might also contribute to the lower levels of HBV activity frequently found in co-infected hepatocytes.",
author = "Katja Giersch and Lena Allweiss and Tassilo Volz and Martina Helbig and Jeanette Bierwolf and Lohse, {Ansgar W} and Pollok, {Joerg M} and Joerg Petersen and Maura Dandri-Petersen and Marc L{\"u}tgehetmann",
note = "Copyright {\textcopyright} 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.",
year = "2015",
month = aug,
doi = "10.1016/j.jhep.2015.03.011",
language = "English",
volume = "63",
pages = "346--53",
journal = "J HEPATOL",
issn = "0168-8278",
publisher = "Elsevier",
number = "2",

}

RIS

TY - JOUR

T1 - Hepatitis Delta co-infection in humanized mice leads to pronounced induction of innate immune responses in comparison to HBV mono-infection

AU - Giersch, Katja

AU - Allweiss, Lena

AU - Volz, Tassilo

AU - Helbig, Martina

AU - Bierwolf, Jeanette

AU - Lohse, Ansgar W

AU - Pollok, Joerg M

AU - Petersen, Joerg

AU - Dandri-Petersen, Maura

AU - Lütgehetmann, Marc

N1 - Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

PY - 2015/8

Y1 - 2015/8

N2 - BACKGROUND & AIMS: The limited availability of hepatitis Delta virus (HDV) infection models has hindered studies of interactions between HDV and infected hepatocytes. The aim was to investigate the antiviral state of HDV infected human hepatocytes in the setting of co-infection with hepatitis B virus (HBV) compared to HBV mono-infection using human liver chimeric mice.METHODS: Viral loads, human interferon stimulated genes (hISGs) and cytokines were determined in humanized uPA/SCID/beige (USB) mice by qRT-PCR, ELISA and immunofluorescence.RESULTS: Upon HBV/HDV inoculation, all mice developed viremia, which was accompanied by a significant induction of hISGs (i.e. hISG15, hSTATs, hHLA-E) compared to uninfected mice, while HBV mono-infection led to weaker hISG elevations. In the setting of chronic infection enhancement of innate defense mechanisms was significantly more prominent in HBV/HDV infected mice. Also the induction of human-specific cytokines (hIP10, hTGF-ß, hIFN-ß and hIFN-λ) was detected in HBV/HDV co-infected animals, while levels remained lower or below detection in uninfected and HBV mono-infected mice. Moreover, despite the average increase of hSTAT levels determined in HBV/HDV infected livers, we observed a weaker hSTAT accumulation in nuclei of hepatocytes displaying very high HDAg levels, suggesting that HDAg may in part limit hSTAT signaling.CONCLUSIONS: Establishment of HDV infection provoked a clear enhancement of the antiviral state of the human hepatocytes in chimeric mice. Elevated pre-treatment ISG and interferon levels may directly contribute to inflammation and liver damage, providing a rationale for the more severe course of HDV-associated liver disease. Such antiviral state induction might also contribute to the lower levels of HBV activity frequently found in co-infected hepatocytes.

AB - BACKGROUND & AIMS: The limited availability of hepatitis Delta virus (HDV) infection models has hindered studies of interactions between HDV and infected hepatocytes. The aim was to investigate the antiviral state of HDV infected human hepatocytes in the setting of co-infection with hepatitis B virus (HBV) compared to HBV mono-infection using human liver chimeric mice.METHODS: Viral loads, human interferon stimulated genes (hISGs) and cytokines were determined in humanized uPA/SCID/beige (USB) mice by qRT-PCR, ELISA and immunofluorescence.RESULTS: Upon HBV/HDV inoculation, all mice developed viremia, which was accompanied by a significant induction of hISGs (i.e. hISG15, hSTATs, hHLA-E) compared to uninfected mice, while HBV mono-infection led to weaker hISG elevations. In the setting of chronic infection enhancement of innate defense mechanisms was significantly more prominent in HBV/HDV infected mice. Also the induction of human-specific cytokines (hIP10, hTGF-ß, hIFN-ß and hIFN-λ) was detected in HBV/HDV co-infected animals, while levels remained lower or below detection in uninfected and HBV mono-infected mice. Moreover, despite the average increase of hSTAT levels determined in HBV/HDV infected livers, we observed a weaker hSTAT accumulation in nuclei of hepatocytes displaying very high HDAg levels, suggesting that HDAg may in part limit hSTAT signaling.CONCLUSIONS: Establishment of HDV infection provoked a clear enhancement of the antiviral state of the human hepatocytes in chimeric mice. Elevated pre-treatment ISG and interferon levels may directly contribute to inflammation and liver damage, providing a rationale for the more severe course of HDV-associated liver disease. Such antiviral state induction might also contribute to the lower levels of HBV activity frequently found in co-infected hepatocytes.

U2 - 10.1016/j.jhep.2015.03.011

DO - 10.1016/j.jhep.2015.03.011

M3 - SCORING: Journal article

C2 - 25795587

VL - 63

SP - 346

EP - 353

JO - J HEPATOL

JF - J HEPATOL

SN - 0168-8278

IS - 2

ER -