A5 - Molecular mechanisms of hepatitis B virus persistence in chronically infected human chimeric mice
PD Dr. rer. nat. Maura Dandri
I. Medizinische Klinik und Poliklinik
Approximately 350 Million individuals are chronically infected worldwide with the Hepatitis B Virus (HBV). Chronic infection is due to a weak immune response raised against the virus and to maintenance of the cccDNA minichromosome, the template of viral transcription. Silencing and destabilization of the cccDNA, as well as enhancement of host immune responses are necessary to clear HBV infection.
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By employing humanized uPA mice we investigated kinetics of HBV infection in vivo. We could demonstrate that host factors and therapeutically applied cytokines (peg-IFN-alpha) can directly affect the cccDNA activity.
In the future, we will study mechanisms of cccDNA clearance in regenerating hepatocytes and viral interference with cellular pathways and innate responses. To analyze interactions between HBV and components of the human immune system, new immune competent chimeric mice will be developed.
Figure 2: Generation of humanized uPA/SCID mice for HBV infection studies. After cell transplantation the mouse liver is stably reconstituted with human hepatocytes (histological staining; human hepatocytes in brown) which can be infected with HBV (HBcAg staining in green).
Allweiss L, Volz T, Giersch K, Kah J, Raffa G, Petersen J, Lohse AW, Beninati C, Pollicino T, Urban S, Lütgehetmann M, Dandri M
Proliferation of primary human hepatocytes and prevention of hepatitis B virus reinfection efficiently deplete nuclear cccDNA in vivo
Gut. 2017 Apr 20. pii: gutjnl-2016-312162. doi: 10.1136/gutjnl-2016-312162. [Epub ahead of print]
Allweiss L, Lütgehetmann M, Dandri M
Immunofluorescent Staining for the Detection of the Hepatitis B Core Antigen in Frozen Liver Sections of Human Liver Chimeric Mice
Methods Mol Biol. 2017;1540:135-142. PubMed PMID: 27975313.
Giersch K, Allweiss L, Volz T, Dandri M, Lütgehetmann M
Serum HBV pgRNA as a clinical marker for cccDNA activity
J Hepatol. 2017 Feb;66(2):460-462. doi:10.1016/j.jhep.2016.09.028.