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Capsid-deficient alphaviruses generate propagative infectious microvesicles at the plasma membrane

Alphavirus budding is driven by interactions between nucleocapsids assembled in the cytoplasm and envelope proteins present at the plasma membrane. So far, the expression of capsid and envelope proteins in infected cells has been considered an absolute requirement for alphavirus budding and propagat...

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Autores principales: Ruiz-Guillen, Marta, Gabev, Evgeni, Quetglas, Jose I., Casales, Erkuden, Ballesteros-Briones, María Cristina, Poutou, Joanna, Aranda, Alejandro, Martisova, Eva, Bezunartea, Jaione, Ondiviela, Marina, Prieto, Jesus, Hernandez-Alcoceba, Ruben, Abrescia, Nicola G. A., Smerdou, Cristian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7079800/
https://www.ncbi.nlm.nih.gov/pubmed/27117550
http://dx.doi.org/10.1007/s00018-016-2230-1
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author Ruiz-Guillen, Marta
Gabev, Evgeni
Quetglas, Jose I.
Casales, Erkuden
Ballesteros-Briones, María Cristina
Poutou, Joanna
Aranda, Alejandro
Martisova, Eva
Bezunartea, Jaione
Ondiviela, Marina
Prieto, Jesus
Hernandez-Alcoceba, Ruben
Abrescia, Nicola G. A.
Smerdou, Cristian
author_facet Ruiz-Guillen, Marta
Gabev, Evgeni
Quetglas, Jose I.
Casales, Erkuden
Ballesteros-Briones, María Cristina
Poutou, Joanna
Aranda, Alejandro
Martisova, Eva
Bezunartea, Jaione
Ondiviela, Marina
Prieto, Jesus
Hernandez-Alcoceba, Ruben
Abrescia, Nicola G. A.
Smerdou, Cristian
author_sort Ruiz-Guillen, Marta
collection PubMed
description Alphavirus budding is driven by interactions between nucleocapsids assembled in the cytoplasm and envelope proteins present at the plasma membrane. So far, the expression of capsid and envelope proteins in infected cells has been considered an absolute requirement for alphavirus budding and propagation. In the present study, we show that Semliki Forest virus and Sindbis virus lacking the capsid gene can propagate in mammalian and insect cells. This propagation is mediated by the release of infectious microvesicles (iMVs), which are pleomorphic and have a larger size and density than wild-type virus. iMVs, which contain viral RNA inside and viral envelope proteins on their surface, are released at the plasma membrane and infect cells using the endocytic pathway in a similar way to wild-type virus. iMVs are not pathogenic in immunocompetent mice when injected intravenously, but can infect different organs like lungs and heart. Finally, we also show that alphavirus genomes without capsid can mediate the propagation of heterologous genes, making these vectors potentially interesting for gene therapy or vaccination studies. The minimalist infectious system described in this study shows that a self-replicating RNA able to express membrane proteins with binding and fusion properties is able to propagate, providing some insights into virus evolution. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00018-016-2230-1) contains supplementary material, which is available to authorized users.
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spelling pubmed-70798002020-03-23 Capsid-deficient alphaviruses generate propagative infectious microvesicles at the plasma membrane Ruiz-Guillen, Marta Gabev, Evgeni Quetglas, Jose I. Casales, Erkuden Ballesteros-Briones, María Cristina Poutou, Joanna Aranda, Alejandro Martisova, Eva Bezunartea, Jaione Ondiviela, Marina Prieto, Jesus Hernandez-Alcoceba, Ruben Abrescia, Nicola G. A. Smerdou, Cristian Cell Mol Life Sci Original Article Alphavirus budding is driven by interactions between nucleocapsids assembled in the cytoplasm and envelope proteins present at the plasma membrane. So far, the expression of capsid and envelope proteins in infected cells has been considered an absolute requirement for alphavirus budding and propagation. In the present study, we show that Semliki Forest virus and Sindbis virus lacking the capsid gene can propagate in mammalian and insect cells. This propagation is mediated by the release of infectious microvesicles (iMVs), which are pleomorphic and have a larger size and density than wild-type virus. iMVs, which contain viral RNA inside and viral envelope proteins on their surface, are released at the plasma membrane and infect cells using the endocytic pathway in a similar way to wild-type virus. iMVs are not pathogenic in immunocompetent mice when injected intravenously, but can infect different organs like lungs and heart. Finally, we also show that alphavirus genomes without capsid can mediate the propagation of heterologous genes, making these vectors potentially interesting for gene therapy or vaccination studies. The minimalist infectious system described in this study shows that a self-replicating RNA able to express membrane proteins with binding and fusion properties is able to propagate, providing some insights into virus evolution. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00018-016-2230-1) contains supplementary material, which is available to authorized users. Springer International Publishing 2016-04-27 2016 /pmc/articles/PMC7079800/ /pubmed/27117550 http://dx.doi.org/10.1007/s00018-016-2230-1 Text en © Springer International Publishing 2016 This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
spellingShingle Original Article
Ruiz-Guillen, Marta
Gabev, Evgeni
Quetglas, Jose I.
Casales, Erkuden
Ballesteros-Briones, María Cristina
Poutou, Joanna
Aranda, Alejandro
Martisova, Eva
Bezunartea, Jaione
Ondiviela, Marina
Prieto, Jesus
Hernandez-Alcoceba, Ruben
Abrescia, Nicola G. A.
Smerdou, Cristian
Capsid-deficient alphaviruses generate propagative infectious microvesicles at the plasma membrane
title Capsid-deficient alphaviruses generate propagative infectious microvesicles at the plasma membrane
title_full Capsid-deficient alphaviruses generate propagative infectious microvesicles at the plasma membrane
title_fullStr Capsid-deficient alphaviruses generate propagative infectious microvesicles at the plasma membrane
title_full_unstemmed Capsid-deficient alphaviruses generate propagative infectious microvesicles at the plasma membrane
title_short Capsid-deficient alphaviruses generate propagative infectious microvesicles at the plasma membrane
title_sort capsid-deficient alphaviruses generate propagative infectious microvesicles at the plasma membrane
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7079800/
https://www.ncbi.nlm.nih.gov/pubmed/27117550
http://dx.doi.org/10.1007/s00018-016-2230-1
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