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Spatial-Temporal Patterns of Viral Amplification and Interference Initiated by a Single Infected Cell

When viruses infect their host cells, they can make defective virus-like particles along with intact virus. Cells coinfected with virus and defective particles often exhibit interference with virus growth caused by the competition for resources by defective genomes. Recent reports of the coexistence...

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Autores principales: Akpinar, Fulya, Inankur, Bahar, Yin, John
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4984635/
https://www.ncbi.nlm.nih.gov/pubmed/27279621
http://dx.doi.org/10.1128/JVI.00807-16
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author Akpinar, Fulya
Inankur, Bahar
Yin, John
author_facet Akpinar, Fulya
Inankur, Bahar
Yin, John
author_sort Akpinar, Fulya
collection PubMed
description When viruses infect their host cells, they can make defective virus-like particles along with intact virus. Cells coinfected with virus and defective particles often exhibit interference with virus growth caused by the competition for resources by defective genomes. Recent reports of the coexistence and cotransmission of such defective interfering particles (DIPs) in vivo, across epidemiological length and time scales, suggest a role in viral pathogenesis, but it is not known how DIPs impact infection spread, even under controlled culture conditions. Using fluorescence microscopy, we quantified coinfections of vesicular stomatitis virus (VSV) expressing a fluorescent reporter protein and its DIPs on BHK-21 host cell monolayers. We found that viral gene expression was more delayed, infections spread more slowly, and patterns of spread became more “patchy” with higher DIP inputs to the initial cell. To examine how infection spread might depend on the behavior of the initial coinfected cell, we built a computational model, adapting a cellular automaton (CA) approach to incorporate kinetic data on virus growth for the first time. Specifically, changes in observed patterns of infection spread could be directly linked to previous high-throughput single-cell measures of virus-DIP coinfection. The CA model also provided testable hypotheses on the spatial-temporal distribution of the DIPs, which remain governed by their predator-prey interaction. More generally, this work offers a data-driven computational modeling approach for better understanding of how single infected cells impact the multiround spread of virus infections across cell populations. IMPORTANCE Defective interfering particles (DIPs) compete with intact virus, depleting host cell resources that are essential for virus growth and infection spread. However, it is not known how such competition, strong or weak, ultimately affects the way in which infections spread and cause disease. In this study, we address this unmet need by developing an integrated experimental-computational approach, which sheds new light on how infections spread. We anticipate that our approach will also be useful in the development of DIPs as therapeutic agents to manage the spread of viral infections.
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spelling pubmed-49846352016-09-06 Spatial-Temporal Patterns of Viral Amplification and Interference Initiated by a Single Infected Cell Akpinar, Fulya Inankur, Bahar Yin, John J Virol Genetic Diversity and Evolution When viruses infect their host cells, they can make defective virus-like particles along with intact virus. Cells coinfected with virus and defective particles often exhibit interference with virus growth caused by the competition for resources by defective genomes. Recent reports of the coexistence and cotransmission of such defective interfering particles (DIPs) in vivo, across epidemiological length and time scales, suggest a role in viral pathogenesis, but it is not known how DIPs impact infection spread, even under controlled culture conditions. Using fluorescence microscopy, we quantified coinfections of vesicular stomatitis virus (VSV) expressing a fluorescent reporter protein and its DIPs on BHK-21 host cell monolayers. We found that viral gene expression was more delayed, infections spread more slowly, and patterns of spread became more “patchy” with higher DIP inputs to the initial cell. To examine how infection spread might depend on the behavior of the initial coinfected cell, we built a computational model, adapting a cellular automaton (CA) approach to incorporate kinetic data on virus growth for the first time. Specifically, changes in observed patterns of infection spread could be directly linked to previous high-throughput single-cell measures of virus-DIP coinfection. The CA model also provided testable hypotheses on the spatial-temporal distribution of the DIPs, which remain governed by their predator-prey interaction. More generally, this work offers a data-driven computational modeling approach for better understanding of how single infected cells impact the multiround spread of virus infections across cell populations. IMPORTANCE Defective interfering particles (DIPs) compete with intact virus, depleting host cell resources that are essential for virus growth and infection spread. However, it is not known how such competition, strong or weak, ultimately affects the way in which infections spread and cause disease. In this study, we address this unmet need by developing an integrated experimental-computational approach, which sheds new light on how infections spread. We anticipate that our approach will also be useful in the development of DIPs as therapeutic agents to manage the spread of viral infections. American Society for Microbiology 2016-07-27 /pmc/articles/PMC4984635/ /pubmed/27279621 http://dx.doi.org/10.1128/JVI.00807-16 Text en Copyright © 2016 Akpinar et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (http://creativecommons.org/licenses/by/4.0/) .
spellingShingle Genetic Diversity and Evolution
Akpinar, Fulya
Inankur, Bahar
Yin, John
Spatial-Temporal Patterns of Viral Amplification and Interference Initiated by a Single Infected Cell
title Spatial-Temporal Patterns of Viral Amplification and Interference Initiated by a Single Infected Cell
title_full Spatial-Temporal Patterns of Viral Amplification and Interference Initiated by a Single Infected Cell
title_fullStr Spatial-Temporal Patterns of Viral Amplification and Interference Initiated by a Single Infected Cell
title_full_unstemmed Spatial-Temporal Patterns of Viral Amplification and Interference Initiated by a Single Infected Cell
title_short Spatial-Temporal Patterns of Viral Amplification and Interference Initiated by a Single Infected Cell
title_sort spatial-temporal patterns of viral amplification and interference initiated by a single infected cell
topic Genetic Diversity and Evolution
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4984635/
https://www.ncbi.nlm.nih.gov/pubmed/27279621
http://dx.doi.org/10.1128/JVI.00807-16
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