The feasibility of establishing a hamster model for HBV infection: in vitro evidence

One of the biggest challenges in developing an HBV cure is the lack of immunocompetent animal models susceptible to HBV infection. Developing such models in mice has been unsuccessful due to the absence of a functional HBV receptor, human NTCP (huNTCP), and the defect in supporting viral cccDNA form...

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Published inmBio Vol. 15; no. 11; p. e0261524
Main Authors Zhang, Hu, Liu, Yanan, Liu, Cheng-Der, Wang, Zhongde, Guo, Haitao
Format Journal Article
LanguageEnglish
Published United States American Society for Microbiology 27.09.2024
Subjects
cccDNA
hamster hepatocytes
hepatitis B virus
NTCP
Observation
Virology
cccDNA
hamster hepatocytes
hepatitis B virus
NTCP
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Summary:One of the biggest challenges in developing an HBV cure is the lack of immunocompetent animal models susceptible to HBV infection. Developing such models in mice has been unsuccessful due to the absence of a functional HBV receptor, human NTCP (huNTCP), and the defect in supporting viral cccDNA formation. In search of alternative models, we report herein multiple lines of in vitro evidence for developing a golden Syrian hamster model for HBV infection. We demonstrate that the primary hamster hepatocytes (PHaHs) support HBV replication, transcription, and cccDNA formation, and PHaHs are susceptible to de novo HBV infection in the presence of huNTCP. Furthermore, expressing hamster NTCP with two humanized residues critical for HBV entry renders HepG2 cells permissive to HBV infection. Thus, our work lays a solid foundation for establishing a gene-edited hamster model that expresses humanized NTCP for HBV infection in vivo .
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Hu Zhang and Yanan Liu contributed equally to this article. Author order was determined in order of increasing seniority.
The authors declare no conflict of interest.
ISSN:2150-7511
2150-7511
DOI:10.1128/mbio.02615-24