Published August 3, 2023
| Version v1
Journal article
Open
Modeling suggests that virion production cycles within individual cells is key to understanding acute hepatitis B virus infection kinetics
Creators
- 1. Loyola University Chicago
- 2. Hiroshima University
- 3. University of Chicago
- 4. Université du Québec à Montréal
- 5. Ben-Gurion University
- 6. PhoenixBio Co., Ltd.
Description
Hepatitis B virus (HBV) infection kinetics in immunodeficient mice reconstituted with humanized livers from inoculation to steady state is highly dynamic despite the absence of an adaptive immune response. To recapitulate the multiphasic viral kinetic patterns, we developed an agent-based model that includes intracellular virion production cycles reflecting the cyclic nature of each individual virus lifecycle. The model fits the data well predicting an increase in production cycles initially starting with a long production cycle of 1 virion per 20 hours that gradually reaches 1 virion per hour after approximately 3–4 days before virion production increases dramatically to reach to a steady state rate of 4 virions per hour per cell. Together, modeling suggests that it is the cyclic nature of the virus lifecycle combined with an initial slow but increasing rate of HBV production from each cell that plays a role in generating the observed multiphasic HBV kinetic patterns in humanized mice.
Data availability
The experimental data is provided in Table A in S1 Text. The agent-based modeling code is available on GitHub (https://github.com/szztracy/ModelingHBVKineticsInMice). We provide a link to run the agent-based model from a web browser: https://cloud.anylogic.com/model/9e9b5f21-01c0-41a7-8b6b-793808d1c6ea?mode=SETTINGS.
Files
journal.pcbi.1011309.pdf
Files
(19.8 MB)
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Additional details
Identifiers
- DOI
- 10.1371/journal.pcbi.1011309
- Other
- oai:uchicago.tind.io:7280
Funding
- National Institutes of Allergy and Infectious Diseases
- R01AI144112
- National Institutes of Allergy and Infectious Diseases
- R01AI146917
- Japan Agency for Medical Research and Development
- 19fk0210020h0003
- Japan Society for the Promotion of Science
- 17KK0194