Modeling suggests that virion production cycles within individual cells is key to understanding acute hepatitis B virus infection kinetics
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Published:2023-08-03
Issue:8
Volume:19
Page:e1011309
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ISSN:1553-7358
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Container-title:PLOS Computational Biology
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language:en
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Short-container-title:PLoS Comput Biol
Author:
Hailegiorgis Atesmachew,
Ishida Yuji,
Collier NicholsonORCID,
Imamura Michio,
Shi Zhenzhen,
Reinharz Vladimir,
Tsuge Masataka,
Barash Danny,
Hiraga Nobuhiko,
Yokomichi Hiroshi,
Tateno Chise,
Ozik JonathanORCID,
Uprichard Susan L.,
Chayama KazuakiORCID,
Dahari HarelORCID
Abstract
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.
Funder
United States National Institutes of Allergy and Infectious Diseases
Japan Agency for Medical Research and Development
Japan Society for the Promotion of Science
Publisher
Public Library of Science (PLoS)
Subject
Computational Theory and Mathematics,Cellular and Molecular Neuroscience,Genetics,Molecular Biology,Ecology,Modeling and Simulation,Ecology, Evolution, Behavior and Systematics
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