African swine fever virus transmembrane protein pEP84R guides core assembly
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2023-01-30
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| Online Access: | http://hdl.handle.net/10261/331466 http://dx.doi.org/10.13039/501100000780 http://dx.doi.org/10.13039/100012818 http://dx.doi.org/10.13039/501100011033 http://dx.doi.org/10.13039/501100004837 https://api.elsevier.com/content/abstract/scopus_id/85147834324 |
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dig-inia-es-10261-3314662023-08-04T20:36:24Z African swine fever virus transmembrane protein pEP84R guides core assembly Alejo, Alí García-Castey, Mayte Guerra Rodriguez, Milagros Hernáez, B. Martín, Verónica Matamoros, Tania Andrés, Germán Agencia Estatal de Investigación (España) Ministerio de Ciencia e Innovación (España) European Commission Comunidad de Madrid Alejo, Alí [0000-0002-1613-6063] García-Castey, Mayte [0000-0001-8531-3353] Guerra Rodriguez, Milagros [0000-0001-5236-6459] Hernáez, B. [0000-0002-4351-0102] Matamoros, Tania [0000-0001-9268-0696] Andrés, Germán [0000-0003-0265-5409] 28 Pág. 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. This work was supported by grants PGC2018-098701-B-I00 (GA) and PID2021-126791NB-I00 (GA and AA), both funded by MCIN/AEI/10.13039/501100011033 with support of “ERDF A way of making Europe”. GA was supported by the ‘Amarouto Program for senior scientists from Comunidad Autónoma de Madrid. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Peer reviewed 2023-07-20T10:32:31Z 2023-07-20T10:32:31Z 2023-01-30 artículo http://purl.org/coar/resource_type/c_6501 PLoS Pathogens 19(1): ee1011136 (2023) 1553-7366 http://hdl.handle.net/10261/331466 10.1371/journal.ppat.1011136 1553-7374 http://dx.doi.org/10.13039/501100000780 http://dx.doi.org/10.13039/100012818 http://dx.doi.org/10.13039/501100011033 http://dx.doi.org/10.13039/501100004837 36716344 2-s2.0-85147834324 https://api.elsevier.com/content/abstract/scopus_id/85147834324 en #PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PGC2018-098701-B-I00/ES/BASES MOLECULARES DE LA ENTRADA Y LA SALIDA DEL VIRUS DE LA PESTE PORCINA AFRICANA/ info:eu-repo/grantAgreement/AEI//PID2021-126791NB-I00 Centro de Investigación en Sanidad Animal (CISA) Publisher's version https://doi.org/10.1371/journal.ppat.1011136 Sí open application/pdf Public Library of Science |
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28 Pág. |
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Agencia Estatal de Investigación (España) Alejo, Alí García-Castey, Mayte Guerra Rodriguez, Milagros Hernáez, B. Martín, Verónica Matamoros, Tania Andrés, Germán |
| format |
artículo |
| author |
Alejo, Alí García-Castey, Mayte Guerra Rodriguez, Milagros Hernáez, B. Martín, Verónica Matamoros, Tania Andrés, Germán |
| spellingShingle |
Alejo, Alí García-Castey, Mayte Guerra Rodriguez, Milagros Hernáez, B. Martín, Verónica Matamoros, Tania Andrés, Germán African swine fever virus transmembrane protein pEP84R guides core assembly |
| author_sort |
Alejo, Alí |
| title |
African swine fever virus transmembrane protein pEP84R guides core assembly |
| title_short |
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_sort |
african swine fever virus transmembrane protein pep84r guides core assembly |
| publisher |
Public Library of Science |
| publishDate |
2023-01-30 |
| url |
http://hdl.handle.net/10261/331466 http://dx.doi.org/10.13039/501100000780 http://dx.doi.org/10.13039/100012818 http://dx.doi.org/10.13039/501100011033 http://dx.doi.org/10.13039/501100004837 https://api.elsevier.com/content/abstract/scopus_id/85147834324 |
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