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African swine fever virus transmembrane protein pEP84R guides core assembly

African swine fever virus (ASFV) causes a devastating hemorrhagic disease with worldwide circulation and no widely available therapeutic prevention. The infectious particle has a multilayered architecture that is articulated upon an endoplasmic reticulum (ER)-derived inner envelope. This membrane ac...

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Autores principales: Alejo, Alí, García-Castey, Mayte, Guerra, Milagros, Hernáez, Bruno, Martín, Verónica, Matamoros, Tania, Andrés, Germán
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9910796/
https://www.ncbi.nlm.nih.gov/pubmed/36716344
http://dx.doi.org/10.1371/journal.ppat.1011136
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author Alejo, Alí
García-Castey, Mayte
Guerra, Milagros
Hernáez, Bruno
Martín, Verónica
Matamoros, Tania
Andrés, Germán
author_facet Alejo, Alí
García-Castey, Mayte
Guerra, Milagros
Hernáez, Bruno
Martín, Verónica
Matamoros, Tania
Andrés, Germán
author_sort Alejo, Alí
collection PubMed
description African swine fever virus (ASFV) causes a devastating hemorrhagic disease with worldwide circulation and no widely available therapeutic prevention. The infectious particle has a multilayered architecture that is articulated upon an endoplasmic reticulum (ER)-derived inner envelope. This membrane acts as docking platform for the assembly of the outer icosahedral capsid and the underlying core shell, a bridging layer required for the formation of the central genome-containing nucleoid. While the details of outer capsid assembly are relatively well understood, those of core formation remain unclear. Here we report the functional characterization of pEP84R, a transmembrane polypeptide embedded in the inner envelope that surrounds the viral core. Using an ASFV recombinant inducibly expressing the EP84R gene, we show that absence of pEP84R results in the formation of non-infectious core-less icosahedral particles displaying a significant DNA-packaging defect. Concomitantly, aberrant core shell-like structures formed by co-assembly of viral polyproteins pp220 and pp62 are mistargeted to non-ER membranes, as also occurs when these are co-expressed in the absence of other viral proteins. Interestingly, co-expression of both polyproteins with pEP84R led to the formation of ER-targeted core shell-like assemblies and co-immunoprecipitation assays showed that pEP84R binds to the N-terminal region of pp220. Altogether, these results indicate that pEP84R plays a crucial role in core assembly by targeting the core shell polyproteins to the inner viral envelope, which enables subsequent genome packaging and nucleoid formation. These findings unveil a key regulatory mechanism for ASFV morphogenesis and identify a relevant novel target for the development of therapeutic tools against this re-emerging threat.
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spelling pubmed-99107962023-02-10 African swine fever virus transmembrane protein pEP84R guides core assembly Alejo, Alí García-Castey, Mayte Guerra, Milagros Hernáez, Bruno Martín, Verónica Matamoros, Tania Andrés, Germán PLoS Pathog Research Article African swine fever virus (ASFV) causes a devastating hemorrhagic disease with worldwide circulation and no widely available therapeutic prevention. The infectious particle has a multilayered architecture that is articulated upon an endoplasmic reticulum (ER)-derived inner envelope. This membrane acts as docking platform for the assembly of the outer icosahedral capsid and the underlying core shell, a bridging layer required for the formation of the central genome-containing nucleoid. While the details of outer capsid assembly are relatively well understood, those of core formation remain unclear. Here we report the functional characterization of pEP84R, a transmembrane polypeptide embedded in the inner envelope that surrounds the viral core. Using an ASFV recombinant inducibly expressing the EP84R gene, we show that absence of pEP84R results in the formation of non-infectious core-less icosahedral particles displaying a significant DNA-packaging defect. Concomitantly, aberrant core shell-like structures formed by co-assembly of viral polyproteins pp220 and pp62 are mistargeted to non-ER membranes, as also occurs when these are co-expressed in the absence of other viral proteins. Interestingly, co-expression of both polyproteins with pEP84R led to the formation of ER-targeted core shell-like assemblies and co-immunoprecipitation assays showed that pEP84R binds to the N-terminal region of pp220. Altogether, these results indicate that pEP84R plays a crucial role in core assembly by targeting the core shell polyproteins to the inner viral envelope, which enables subsequent genome packaging and nucleoid formation. These findings unveil a key regulatory mechanism for ASFV morphogenesis and identify a relevant novel target for the development of therapeutic tools against this re-emerging threat. Public Library of Science 2023-01-30 /pmc/articles/PMC9910796/ /pubmed/36716344 http://dx.doi.org/10.1371/journal.ppat.1011136 Text en © 2023 Alejo et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://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
Alejo, Alí
García-Castey, Mayte
Guerra, Milagros
Hernáez, Bruno
Martín, Verónica
Matamoros, Tania
Andrés, Germán
African swine fever virus transmembrane protein pEP84R guides core assembly
title African swine fever virus transmembrane protein pEP84R guides core assembly
title_full African swine fever virus transmembrane protein pEP84R guides core assembly
title_fullStr African swine fever virus transmembrane protein pEP84R guides core assembly
title_full_unstemmed African swine fever virus transmembrane protein pEP84R guides core assembly
title_short African swine fever virus transmembrane protein pEP84R guides core assembly
title_sort african swine fever virus transmembrane protein pep84r guides core assembly
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9910796/
https://www.ncbi.nlm.nih.gov/pubmed/36716344
http://dx.doi.org/10.1371/journal.ppat.1011136
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