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Modeling suggests that virion production cycles within individual cells is key to understanding acute hepatitis B virus infection kinetics

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...

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Autores principales: Hailegiorgis, Atesmachew, Ishida, Yuji, Collier, Nicholson, Imamura, Michio, Shi, Zhenzhen, Reinharz, Vladimir, Tsuge, Masataka, Barash, Danny, Hiraga, Nobuhiko, Yokomichi, Hiroshi, Tateno, Chise, Ozik, Jonathan, Uprichard, Susan L., Chayama, Kazuaki, Dahari, Harel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10426918/
https://www.ncbi.nlm.nih.gov/pubmed/37535676
http://dx.doi.org/10.1371/journal.pcbi.1011309
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author Hailegiorgis, Atesmachew
Ishida, Yuji
Collier, Nicholson
Imamura, Michio
Shi, Zhenzhen
Reinharz, Vladimir
Tsuge, Masataka
Barash, Danny
Hiraga, Nobuhiko
Yokomichi, Hiroshi
Tateno, Chise
Ozik, Jonathan
Uprichard, Susan L.
Chayama, Kazuaki
Dahari, Harel
author_facet Hailegiorgis, Atesmachew
Ishida, Yuji
Collier, Nicholson
Imamura, Michio
Shi, Zhenzhen
Reinharz, Vladimir
Tsuge, Masataka
Barash, Danny
Hiraga, Nobuhiko
Yokomichi, Hiroshi
Tateno, Chise
Ozik, Jonathan
Uprichard, Susan L.
Chayama, Kazuaki
Dahari, Harel
author_sort Hailegiorgis, Atesmachew
collection PubMed
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.
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spelling pubmed-104269182023-08-16 Modeling suggests that virion production cycles within individual cells is key to understanding acute hepatitis B virus infection kinetics Hailegiorgis, Atesmachew Ishida, Yuji Collier, Nicholson Imamura, Michio Shi, Zhenzhen Reinharz, Vladimir Tsuge, Masataka Barash, Danny Hiraga, Nobuhiko Yokomichi, Hiroshi Tateno, Chise Ozik, Jonathan Uprichard, Susan L. Chayama, Kazuaki Dahari, Harel PLoS Comput Biol Research Article 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. Public Library of Science 2023-08-03 /pmc/articles/PMC10426918/ /pubmed/37535676 http://dx.doi.org/10.1371/journal.pcbi.1011309 Text en https://creativecommons.org/publicdomain/zero/1.0/This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication.
spellingShingle Research Article
Hailegiorgis, Atesmachew
Ishida, Yuji
Collier, Nicholson
Imamura, Michio
Shi, Zhenzhen
Reinharz, Vladimir
Tsuge, Masataka
Barash, Danny
Hiraga, Nobuhiko
Yokomichi, Hiroshi
Tateno, Chise
Ozik, Jonathan
Uprichard, Susan L.
Chayama, Kazuaki
Dahari, Harel
Modeling suggests that virion production cycles within individual cells is key to understanding acute hepatitis B virus infection kinetics
title Modeling suggests that virion production cycles within individual cells is key to understanding acute hepatitis B virus infection kinetics
title_full Modeling suggests that virion production cycles within individual cells is key to understanding acute hepatitis B virus infection kinetics
title_fullStr Modeling suggests that virion production cycles within individual cells is key to understanding acute hepatitis B virus infection kinetics
title_full_unstemmed Modeling suggests that virion production cycles within individual cells is key to understanding acute hepatitis B virus infection kinetics
title_short Modeling suggests that virion production cycles within individual cells is key to understanding acute hepatitis B virus infection kinetics
title_sort modeling suggests that virion production cycles within individual cells is key to understanding acute hepatitis b virus infection kinetics
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10426918/
https://www.ncbi.nlm.nih.gov/pubmed/37535676
http://dx.doi.org/10.1371/journal.pcbi.1011309
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