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Estimation of virus-mediated cell fusion rate of SARS-CoV-2

Several viruses have the ability to form large multinucleated cells known as syncytia. Many properties of syncytia and the role they play in the evolution of a viral infection are not well understood. One basic question that has not yet been answered is how quickly syncytia form. We use a novel math...

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Detalles Bibliográficos
Autores principales: Amidei, Ava, Dobrovolny, Hana M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9449781/
https://www.ncbi.nlm.nih.gov/pubmed/36088794
http://dx.doi.org/10.1016/j.virol.2022.08.016
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author Amidei, Ava
Dobrovolny, Hana M.
author_facet Amidei, Ava
Dobrovolny, Hana M.
author_sort Amidei, Ava
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description Several viruses have the ability to form large multinucleated cells known as syncytia. Many properties of syncytia and the role they play in the evolution of a viral infection are not well understood. One basic question that has not yet been answered is how quickly syncytia form. We use a novel mathematical model of cell-cell fusion assays and apply it to experimental data from SARS-CoV-2 fusion assays to provide the first estimates of virus-mediated cell fusion rate. We find that for SARS-CoV2, the fusion rate is in the range of 6 × 10(−4)–12×10(−4)/h. We also use our model to compare fusion rates when the protease TMPRSS2 is overexpressed (2–4 times larger fusion rate), when the protease furin is removed (one third the original fusion rate), and when the spike protein is altered (1/10th the original fusion rate). The use of mathematical models allows us to provide additional quantitative information about syncytia formation.
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spelling pubmed-94497812022-09-07 Estimation of virus-mediated cell fusion rate of SARS-CoV-2 Amidei, Ava Dobrovolny, Hana M. Virology Article Several viruses have the ability to form large multinucleated cells known as syncytia. Many properties of syncytia and the role they play in the evolution of a viral infection are not well understood. One basic question that has not yet been answered is how quickly syncytia form. We use a novel mathematical model of cell-cell fusion assays and apply it to experimental data from SARS-CoV-2 fusion assays to provide the first estimates of virus-mediated cell fusion rate. We find that for SARS-CoV2, the fusion rate is in the range of 6 × 10(−4)–12×10(−4)/h. We also use our model to compare fusion rates when the protease TMPRSS2 is overexpressed (2–4 times larger fusion rate), when the protease furin is removed (one third the original fusion rate), and when the spike protein is altered (1/10th the original fusion rate). The use of mathematical models allows us to provide additional quantitative information about syncytia formation. Elsevier Inc. 2022-10 2022-09-07 /pmc/articles/PMC9449781/ /pubmed/36088794 http://dx.doi.org/10.1016/j.virol.2022.08.016 Text en © 2022 Elsevier Inc. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
Amidei, Ava
Dobrovolny, Hana M.
Estimation of virus-mediated cell fusion rate of SARS-CoV-2
title Estimation of virus-mediated cell fusion rate of SARS-CoV-2
title_full Estimation of virus-mediated cell fusion rate of SARS-CoV-2
title_fullStr Estimation of virus-mediated cell fusion rate of SARS-CoV-2
title_full_unstemmed Estimation of virus-mediated cell fusion rate of SARS-CoV-2
title_short Estimation of virus-mediated cell fusion rate of SARS-CoV-2
title_sort estimation of virus-mediated cell fusion rate of sars-cov-2
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9449781/
https://www.ncbi.nlm.nih.gov/pubmed/36088794
http://dx.doi.org/10.1016/j.virol.2022.08.016
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