Z Gastroenterol 2023; 61(01): e48
DOI: 10.1055/s-0042-1760050
Abstracts | GASL
Poster Visit Session V Viral Hepatitis and Immunology 28/01/2023, 11.00 am – 11.45 am

Characterization of viral replication in different Hepatitis B virus-transgenic mice and its impact on antiviral signalling in vivo

Stefan Schefczyk
1   University Medicine Essen
,
Xufeng Luo
2   The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital
,
Aojie Liang
1   University Medicine Essen
,
Mike Hasenberg
3   University of Duisburg-Essen
,
Bernd Walkenfort
3   University of Duisburg-Essen
,
Simon Merz
4   LaVision BioTec GmbH, Bielefeld
,
Lea Bornemann
4   LaVision BioTec GmbH, Bielefeld
,
Martin Trippler
1   University Medicine Essen
,
Mengji Lu
3   University of Duisburg-Essen
,
Heiner Wedemeyer
5   Hannover Medical School
,
HartmutH. Schmidt
1   University Medicine Essen
,
Ruth Broering
1   University Medicine Essen
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    Background & Aims Pathogenesis of hepatitis B virus (HBV) infection is driven by innate and adaptive immunity. One aim of this study was to investigate how hepatitis B surface antigen (HBsAg) affects intrinsic antiviral signalling in HBV-transgenic mouse models that accumulate, lack or secrete the HBsAg. Another aim was to investigate how HBV HBsAg affects Kupffer cell populations in the different HBV-transgenic mouse strains.

    Methods Liver tissue from C57/Bl6 and HBV-transgenic mouse strains (tg(Alb1HBV)44Bri (Alb/HBs), tg1.4HBV-s-mut and tg1.4HBV-s-rec [F1 generation of Alb/HBs×tg1.4HBV-s-mut]) was analysed using transmission electron microscopy (TEM) and confocal microscopy. HBV replication was characterized on RNA and protein level. Further F4/80 staining was performed in ECi cleared liver tissue and visualised by Light sheet fluorescence microscopy (LSFM). Responsiveness of parenchymal and non-parenchymal liver cells to poly(I:C) treatment in vivo was determined using quantitative RT-PCR and multiplex-based cytokine assay.

    Results TEM visualised viral particles (Tg1.4HBV-s-rec), nuclear circular formations (Tg1.4HBV-s-mut and Tg1.4HBV-s-rec) and malformation of the endoplasmic reticulum (Alb/HBs). Confocal microscopy visualised HBsAg and HBcAg distribution in hepatocytes of HBV-transgenic mouse strains. Viral replication did not differ between Tg1.4HBV-s-rec and Tg1.4HBV-s-mut, except HBsAg levels. LSFM visualised a different intensity and volume of F4/80 positive cells in the liver of HBV transgenic mice. Cell type-specific and mouse strain-dependent interferon, cytokine, and chemokine expression were observed by LEGENDplex™ analysis.

    Conclusion Liver cells of Tg1.4HBV-s-rec mice, which produce HBV particles and release HBsAg, exhibited a tolerogenic environment in vivo. Viral replication influences the distribution, size and intensity of F4/80 positive cells.


     

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    Artikel online veröffentlicht:
    18. Januar 2023

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