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Title: Should a viral genome stay in the host cell or leave? A quantitative dynamics study of how hepatitis C virus deals with this dilemma
Authors: Iwanami, Shoya
Kitagawa, Kosaku
Ohashi, Hirofumi
Asai, Yusuke
Shionoya, Kaho
Saso, Wakana
Nishioka, Kazane
Inaba, Hisashi
Nakaoka, Shinji
Wakita, Takaji
Diekmann, Odo
Iwami, Shingo
Watashi, Koichi
Author's alias: 岩波, 翔也
北川, 耕咲
大橋, 啓史
浅井, 雄介
佐宗, 若奈
西岡, 華実
稲葉, 寿
中岡, 慎治
脇田, 隆字
岩見, 真吾
渡士, 幸一
Issue Date: 30-Jul-2020
Publisher: Public Library of Science (PLoS)
Journal title: PLOS Biology
Volume: 18
Issue: 7
Thesis number: e3000562
Abstract: Virus proliferation involves gene replication inside infected cells and transmission to new target cells. Once positive-strand RNA virus has infected a cell, the viral genome serves as a template for copying (“stay-strategy”) or is packaged into a progeny virion that will be released extracellularly (“leave-strategy”). The balance between genome replication and virion release determines virus production and transmission efficacy. The ensuing trade-off has not yet been well characterized. In this study, we use hepatitis C virus (HCV) as a model system to study the balance of the two strategies. Combining viral infection cell culture assays with mathematical modeling, we characterize the dynamics of two different HCV strains (JFH-1, a clinical isolate, and Jc1-n, a laboratory strain), which have different viral release characteristics. We found that 0.63% and 1.70% of JFH-1 and Jc1-n intracellular viral RNAs, respectively, are used for producing and releasing progeny virions. Analysis of the Malthusian parameter of the HCV genome (i.e., initial proliferation rate) and the number of de novo infections (i.e., initial transmissibility) suggests that the leave-strategy provides a higher level of initial transmission for Jc1-n, whereas, in contrast, the stay-strategy provides a higher initial proliferation rate for JFH-1. Thus, theoretical-experimental analysis of viral dynamics enables us to better understand the proliferation strategies of viruses, which contributes to the efficient control of virus transmission. Ours is the first study to analyze the stay-leave trade-off during the viral life cycle and the significance of the replication-release switching mechanism for viral proliferation.
Description: 数学と実験の融合研究でC型肝炎ウイルスの感染戦略を解明 --ウイルスは、インドア派かアウトドア派か--. 京都大学プレスリリース. 2020-07-31.
Rights: © 2020 Iwanami et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI(Published Version): 10.1371/journal.pbio.3000562
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