Equine rhinitis A virus and its low pH empty particle: clues towards an aphthovirus entry mechanism?

Equine rhinitis A virus (ERAV) is closely related to foot-and-mouth disease virus (FMDV), belonging to the genus Aphthovirus of the Picornaviridae. How picornaviruses introduce their RNA genome into the cytoplasm of the host cell to initiate replication is unclear since they have no lipid envelope t...

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Autores principales:	Tobias J Tuthill, Karl Harlos, Thomas S Walter, Nick J Knowles, Elisabetta Groppelli, David J Rowlands, David I Stuart, Elizabeth E Fry
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/66f5b04743c946ecbf6520d017d294da
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spelling	oai:doaj.org-article:66f5b04743c946ecbf6520d017d294da2021-12-02T19:59:45ZEquine rhinitis A virus and its low pH empty particle: clues towards an aphthovirus entry mechanism?1553-73661553-737410.1371/journal.ppat.1000620https://doaj.org/article/66f5b04743c946ecbf6520d017d294da2009-10-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19816570/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Equine rhinitis A virus (ERAV) is closely related to foot-and-mouth disease virus (FMDV), belonging to the genus Aphthovirus of the Picornaviridae. How picornaviruses introduce their RNA genome into the cytoplasm of the host cell to initiate replication is unclear since they have no lipid envelope to facilitate fusion with cellular membranes. It has been thought that the dissociation of the FMDV particle into pentameric subunits at acidic pH is the mechanism for genome release during cell entry, but this raises the problem of how transfer across the endosome membrane of the genome might be facilitated. In contrast, most other picornaviruses form 'altered' particle intermediates (not reported for aphthoviruses) thought to induce membrane pores through which the genome can be transferred. Here we show that ERAV, like FMDV, dissociates into pentamers at mildly acidic pH but demonstrate that dissociation is preceded by the transient formation of empty 80S particles which have released their genome and may represent novel biologically relevant intermediates in the aphthovirus cell entry process. The crystal structures of the native ERAV virus and a low pH form have been determined via highly efficient crystallization and data collection strategies, required due to low virus yields. ERAV is closely similar to FMDV for VP2, VP3 and part of VP4 but VP1 diverges, to give a particle with a pitted surface, as seen in cardioviruses. The low pH particle has internal structure consistent with it representing a pre-dissociation cell entry intermediate. These results suggest a unified mechanism of picornavirus cell entry.Tobias J TuthillKarl HarlosThomas S WalterNick J KnowlesElisabetta GroppelliDavid J RowlandsDavid I StuartElizabeth E FryPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 5, Iss 10, p e1000620 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Tobias J Tuthill Karl Harlos Thomas S Walter Nick J Knowles Elisabetta Groppelli David J Rowlands David I Stuart Elizabeth E Fry Equine rhinitis A virus and its low pH empty particle: clues towards an aphthovirus entry mechanism?
description	Equine rhinitis A virus (ERAV) is closely related to foot-and-mouth disease virus (FMDV), belonging to the genus Aphthovirus of the Picornaviridae. How picornaviruses introduce their RNA genome into the cytoplasm of the host cell to initiate replication is unclear since they have no lipid envelope to facilitate fusion with cellular membranes. It has been thought that the dissociation of the FMDV particle into pentameric subunits at acidic pH is the mechanism for genome release during cell entry, but this raises the problem of how transfer across the endosome membrane of the genome might be facilitated. In contrast, most other picornaviruses form 'altered' particle intermediates (not reported for aphthoviruses) thought to induce membrane pores through which the genome can be transferred. Here we show that ERAV, like FMDV, dissociates into pentamers at mildly acidic pH but demonstrate that dissociation is preceded by the transient formation of empty 80S particles which have released their genome and may represent novel biologically relevant intermediates in the aphthovirus cell entry process. The crystal structures of the native ERAV virus and a low pH form have been determined via highly efficient crystallization and data collection strategies, required due to low virus yields. ERAV is closely similar to FMDV for VP2, VP3 and part of VP4 but VP1 diverges, to give a particle with a pitted surface, as seen in cardioviruses. The low pH particle has internal structure consistent with it representing a pre-dissociation cell entry intermediate. These results suggest a unified mechanism of picornavirus cell entry.
format	article
author	Tobias J Tuthill Karl Harlos Thomas S Walter Nick J Knowles Elisabetta Groppelli David J Rowlands David I Stuart Elizabeth E Fry
author_facet	Tobias J Tuthill Karl Harlos Thomas S Walter Nick J Knowles Elisabetta Groppelli David J Rowlands David I Stuart Elizabeth E Fry
author_sort	Tobias J Tuthill
title	Equine rhinitis A virus and its low pH empty particle: clues towards an aphthovirus entry mechanism?
title_short	Equine rhinitis A virus and its low pH empty particle: clues towards an aphthovirus entry mechanism?
title_full	Equine rhinitis A virus and its low pH empty particle: clues towards an aphthovirus entry mechanism?
title_fullStr	Equine rhinitis A virus and its low pH empty particle: clues towards an aphthovirus entry mechanism?
title_full_unstemmed	Equine rhinitis A virus and its low pH empty particle: clues towards an aphthovirus entry mechanism?
title_sort	equine rhinitis a virus and its low ph empty particle: clues towards an aphthovirus entry mechanism?
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/66f5b04743c946ecbf6520d017d294da
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Equine rhinitis A virus and its low pH empty particle: clues towards an aphthovirus entry mechanism?

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