Cargando…
A unifying structural and functional model of the coronavirus replication organelle: Tracking down RNA synthesis
Zoonotic coronavirus (CoV) infections, such as those responsible for the current severe acute respiratory syndrome-CoV 2 (SARS-CoV-2) pandemic, cause grave international public health concern. In infected cells, the CoV RNA-synthesizing machinery associates with modified endoplasmic reticulum membra...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7302735/ https://www.ncbi.nlm.nih.gov/pubmed/32511245 http://dx.doi.org/10.1371/journal.pbio.3000715 |
_version_ | 1783547911293894656 |
---|---|
author | Snijder, Eric J. Limpens, Ronald W. A. L. de Wilde, Adriaan H. de Jong, Anja W. M. Zevenhoven-Dobbe, Jessika C. Maier, Helena J. Faas, Frank F. G. A. Koster, Abraham J. Bárcena, Montserrat |
author_facet | Snijder, Eric J. Limpens, Ronald W. A. L. de Wilde, Adriaan H. de Jong, Anja W. M. Zevenhoven-Dobbe, Jessika C. Maier, Helena J. Faas, Frank F. G. A. Koster, Abraham J. Bárcena, Montserrat |
author_sort | Snijder, Eric J. |
collection | PubMed |
description | Zoonotic coronavirus (CoV) infections, such as those responsible for the current severe acute respiratory syndrome-CoV 2 (SARS-CoV-2) pandemic, cause grave international public health concern. In infected cells, the CoV RNA-synthesizing machinery associates with modified endoplasmic reticulum membranes that are transformed into the viral replication organelle (RO). Although double-membrane vesicles (DMVs) appear to be a pan-CoV RO element, studies to date describe an assortment of additional CoV-induced membrane structures. Despite much speculation, it remains unclear which RO element(s) accommodate viral RNA synthesis. Here we provide detailed 2D and 3D analyses of CoV ROs and show that diverse CoVs essentially induce the same membrane modifications, including the small open double-membrane spherules (DMSs) previously thought to be restricted to gamma- and delta-CoV infections and proposed as sites of replication. Metabolic labeling of newly synthesized viral RNA followed by quantitative electron microscopy (EM) autoradiography revealed abundant viral RNA synthesis associated with DMVs in cells infected with the beta-CoVs Middle East respiratory syndrome-CoV (MERS-CoV) and SARS-CoV and the gamma-CoV infectious bronchitis virus. RNA synthesis could not be linked to DMSs or any other cellular or virus-induced structure. Our results provide a unifying model of the CoV RO and clearly establish DMVs as the central hub for viral RNA synthesis and a potential drug target in CoV infection. |
format | Online Article Text |
id | pubmed-7302735 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-73027352020-06-19 A unifying structural and functional model of the coronavirus replication organelle: Tracking down RNA synthesis Snijder, Eric J. Limpens, Ronald W. A. L. de Wilde, Adriaan H. de Jong, Anja W. M. Zevenhoven-Dobbe, Jessika C. Maier, Helena J. Faas, Frank F. G. A. Koster, Abraham J. Bárcena, Montserrat PLoS Biol Research Article Zoonotic coronavirus (CoV) infections, such as those responsible for the current severe acute respiratory syndrome-CoV 2 (SARS-CoV-2) pandemic, cause grave international public health concern. In infected cells, the CoV RNA-synthesizing machinery associates with modified endoplasmic reticulum membranes that are transformed into the viral replication organelle (RO). Although double-membrane vesicles (DMVs) appear to be a pan-CoV RO element, studies to date describe an assortment of additional CoV-induced membrane structures. Despite much speculation, it remains unclear which RO element(s) accommodate viral RNA synthesis. Here we provide detailed 2D and 3D analyses of CoV ROs and show that diverse CoVs essentially induce the same membrane modifications, including the small open double-membrane spherules (DMSs) previously thought to be restricted to gamma- and delta-CoV infections and proposed as sites of replication. Metabolic labeling of newly synthesized viral RNA followed by quantitative electron microscopy (EM) autoradiography revealed abundant viral RNA synthesis associated with DMVs in cells infected with the beta-CoVs Middle East respiratory syndrome-CoV (MERS-CoV) and SARS-CoV and the gamma-CoV infectious bronchitis virus. RNA synthesis could not be linked to DMSs or any other cellular or virus-induced structure. Our results provide a unifying model of the CoV RO and clearly establish DMVs as the central hub for viral RNA synthesis and a potential drug target in CoV infection. Public Library of Science 2020-06-08 /pmc/articles/PMC7302735/ /pubmed/32511245 http://dx.doi.org/10.1371/journal.pbio.3000715 Text en © 2020 Snijder et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Snijder, Eric J. Limpens, Ronald W. A. L. de Wilde, Adriaan H. de Jong, Anja W. M. Zevenhoven-Dobbe, Jessika C. Maier, Helena J. Faas, Frank F. G. A. Koster, Abraham J. Bárcena, Montserrat A unifying structural and functional model of the coronavirus replication organelle: Tracking down RNA synthesis |
title | A unifying structural and functional model of the coronavirus replication organelle: Tracking down RNA synthesis |
title_full | A unifying structural and functional model of the coronavirus replication organelle: Tracking down RNA synthesis |
title_fullStr | A unifying structural and functional model of the coronavirus replication organelle: Tracking down RNA synthesis |
title_full_unstemmed | A unifying structural and functional model of the coronavirus replication organelle: Tracking down RNA synthesis |
title_short | A unifying structural and functional model of the coronavirus replication organelle: Tracking down RNA synthesis |
title_sort | unifying structural and functional model of the coronavirus replication organelle: tracking down rna synthesis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7302735/ https://www.ncbi.nlm.nih.gov/pubmed/32511245 http://dx.doi.org/10.1371/journal.pbio.3000715 |
work_keys_str_mv | AT snijderericj aunifyingstructuralandfunctionalmodelofthecoronavirusreplicationorganelletrackingdownrnasynthesis AT limpensronaldwal aunifyingstructuralandfunctionalmodelofthecoronavirusreplicationorganelletrackingdownrnasynthesis AT dewildeadriaanh aunifyingstructuralandfunctionalmodelofthecoronavirusreplicationorganelletrackingdownrnasynthesis AT dejonganjawm aunifyingstructuralandfunctionalmodelofthecoronavirusreplicationorganelletrackingdownrnasynthesis AT zevenhovendobbejessikac aunifyingstructuralandfunctionalmodelofthecoronavirusreplicationorganelletrackingdownrnasynthesis AT maierhelenaj aunifyingstructuralandfunctionalmodelofthecoronavirusreplicationorganelletrackingdownrnasynthesis AT faasfrankfga aunifyingstructuralandfunctionalmodelofthecoronavirusreplicationorganelletrackingdownrnasynthesis AT kosterabrahamj aunifyingstructuralandfunctionalmodelofthecoronavirusreplicationorganelletrackingdownrnasynthesis AT barcenamontserrat aunifyingstructuralandfunctionalmodelofthecoronavirusreplicationorganelletrackingdownrnasynthesis AT snijderericj unifyingstructuralandfunctionalmodelofthecoronavirusreplicationorganelletrackingdownrnasynthesis AT limpensronaldwal unifyingstructuralandfunctionalmodelofthecoronavirusreplicationorganelletrackingdownrnasynthesis AT dewildeadriaanh unifyingstructuralandfunctionalmodelofthecoronavirusreplicationorganelletrackingdownrnasynthesis AT dejonganjawm unifyingstructuralandfunctionalmodelofthecoronavirusreplicationorganelletrackingdownrnasynthesis AT zevenhovendobbejessikac unifyingstructuralandfunctionalmodelofthecoronavirusreplicationorganelletrackingdownrnasynthesis AT maierhelenaj unifyingstructuralandfunctionalmodelofthecoronavirusreplicationorganelletrackingdownrnasynthesis AT faasfrankfga unifyingstructuralandfunctionalmodelofthecoronavirusreplicationorganelletrackingdownrnasynthesis AT kosterabrahamj unifyingstructuralandfunctionalmodelofthecoronavirusreplicationorganelletrackingdownrnasynthesis AT barcenamontserrat unifyingstructuralandfunctionalmodelofthecoronavirusreplicationorganelletrackingdownrnasynthesis |