Small Supermodel Helps Fighting Hepatitis B

2019 International HBV Meeting “The molecular biology of the hepatitis B virus” took place earlier this year in Melbourne, Australia. The aim of the conference is to bring together scientists from all over the world studying diverse aspects of hepatitis B and D viruses, related animal model viruses, and hepatitis B-induced hepatocellular carcinoma. The meeting emphasizes the work-in-progress by limiting presentations to unpublished data.

It was very rewarding to see significant number of research presentations which use chimeric mice with humanized liver in studies. And even more: most of those presentations used PhoenixBio products (both PXB-mouse® and PXB-cells®) in their work. The total number of oral and poster presentations clearly points to the importance of the model in finding the cure for Hepatitis B.

Hepatitis B: Key Facts

  • WHO estimates that in 2015, 257 million people were living with chronic hepatitis B infection
  • In 2015, hepatitis B resulted in an estimated 887 000 deaths
  • As of 2016, 27 million people (10.5% of all people estimated to be living with hepatitis B) were aware of their infection, while 4.5 million (16.7%) of the people diagnosed were on treatment

Source: https://www.who.int/news-room/fact-sheets/detail/hepatitis-b

One of the oral presentations where in vitro and in vivo data were generated with the use of PXB-cells® and PXB-mice was looking into the inhibition of sodium taurocholate cotransporting polypeptide (NTCP) which is an important HBV receptor. Authors from the National Institute of Infectious Diseases (Tokyo, Japan) hypothesized that bile acid derivatives, which are FXR agonists, would block HBV entry efficiently by inhibiting NTCP. FXR/TGR5 dual agonist severely impaired HBV infection in PXB-cells® and PXB-mice (in HepG2.2.15 cells the inhibitory effect was not observed).

Other presentations are listed below.

In summary, it is important to mention that chimeric mouse showed its usefulness in the development of cure for hepatitis C (HCV) during previous decades. In total, well above 150 compounds were evaluated in uPA/SCID mouse model with humanized liver. With the abundant use of the model in HBV research these days, it would be correct to say that chimeric mice help enormously in current search for the cure for hepatitis B.

Oral presentations

#8 – “Epidermal growth factor receptor as a novel host entry cofactor that triggers hepatitis B virus internalization”
#135 – “Mechanism of viral interference and treatment response in HBV and HCV co-infection”
#271 – “Evaluation of NTCP decoy peptide as an HBV internalization inhibitor through dissociation of EGFR-NTCP complex”
#272 – “FXR/TGR5 dual agonist inhibits hepatitis B virus infection in vitro and in vivo”
#274 – “A Novel CpAM, CBT-078”
#277 – “The activation of RIG-I dependent innate immune responses by HCV poly U/UC PAMP motif inhibits cccDNA formation”

Poster presentations

#29 – “Investigation of infectivity of serum-derived HBV from patients and human hepatocyte chimeric mouse to HepG2/NTCP cells”
#34 – “HBV Infection and spread in HepG2-NTCP cells initiated by low MOI inoculation in the absence of PEG”
#53 – “A small chemical compound CDM-3008 modulates cccDNA and suppresses HBV through induction of interferon-stimulated genes”
#55 – “Hepatitis B virus cccDNA is stable during hepatocyte proliferation in vivo”
#64 – “A novel lntiviral screening of inhibitor of episomal DNA identified dicumarol as an inhibitor of HBV replication”
#86 – “Enhancement of hepatitis B virus replication by a microRNA targeting pregenomic RNA”
#96 – “Analysis of the association between HBV infection and long term trends in intrahepatic gene expression”
#190 – “Comparative proteomics analysis identifies HMGB1 as epigenetic silencer of HBV cccDNA minichromosome”
#227 – “Novel anti-HBV compound, FF-B003, reduced HBV DNA and HBsAg by destabilizing HBV RNA”
#235 – “Receptor tyrosine kinase inhibitors as novel anti-hepatitis B virus entry inhibitors”
#240 – “Development of an in vivo delivery system for CRISPR/Cas9-mediated targeting of hepatitis B virus covalently closed circular DNA”