Modeling of hepatitis B virus kinetics and accumulation of cccDNA in primary human hepatocytes
Using primary human hepatocytes (PHHs), we characterize early HBV kinetics post infection. HBV-infected PHH were treated with an entry inhibitor to characterize the accumulation of intracellular and extracellular HBV DNA and the nuclear episomal viral genome called covalently closed circular DNA (cccDNA) in the absence of HBV spread. Kinetic and mathematical modeling in PHHs confirms that the replication inhibitor, entecavir, strongly blocks intracellular HBV DNA accumulation, which also slowed the accumulation of cccDNA. However, modeling indicates that effects on cccDNA accumulation are not directly determined by intracellular HBV DNA levels, supporting the conclusion that cccDNA levels within the cell are regulated in some yet-to-be-elucidated manner.
Authors
- Chise Tateno (ORCID: https://orcid.org/0000-0002-2640-3268)
- Kazuaki Chayama (ORCID: https://orcid.org/0000-0002-5530-5341)
- Masataka Tsuge (ORCID: https://orcid.org/0000-0001-7591-8287)
- Harel Dahari (ORCID: https://orcid.org/0000-0002-3357-1817)
- Yuji Ishida (ORCID: https://orcid.org/0000-0003-1855-6325)
- Susan L. Uprichard (ORCID: https://orcid.org/0000-0001-5691-1557)
- Masaki Takahashi (ORCID: https://orcid.org/0000-0001-6613-4173)
- Vladimir Reinharz (ORCID: https://orcid.org/0000-0001-8481-1094)
- Louis Shekhtman (ORCID: https://orcid.org/0000-0001-5273-8363)
- Mikaru Yamao
Institutions
- Hiroshima University (JP)
- Loyola University Medical Center (US)
- Bar-Ilan University (IL)
- Université du Québec à Montréal (CA)
- PhoenixBio (Japan) (JP)
- Hiroshima University Hospital (JP)
- RIKEN Center for Integrative Medical Sciences (JP)
Publication Details
- Journal
- JHEP Reports
- Published
- 2024-12-24
- DOI
- https://doi.org/10.1016/j.jhepr.2024.101311
- Citations
- 6
- Primary Topic
- Hepatitis B Virus Studies
- Type
- article
- Field-Weighted Citation Impact
- 2.32
Funders
- Japan Agency for Medical Research and Development
- National Institutes of Health
- Japan Society for the Promotion of Science