Deletion mutants of VPg reveal new cytopathology determinants in a picornavirus.

Background Success of a viral infection requires that each infected cell delivers a sufficient number of infectious particles to allow new rounds of infection. In picornaviruses, viral replication is initiated by the viral polymerase and a viral-coded protein, termed VPg, that primes RNA synthesis....

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Autores: Arias Esteban, Armando, Perales, Celia, Escarmís, Cristina, Domingo, Esteban
Tipo de recurso: artículo
Fecha de publicación:2010
País:España
Institución:Universidad de Castilla-La Mancha
Repositorio:RUIdeRA. Repositorio Institucional de la UCLM
OAI Identifier:oai:ruidera.uclm.es:10578/46900
Acceso en línea:https://hdl.handle.net/10578/46900
Access Level:acceso abierto
Palabra clave:Picornavirus
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spelling Deletion mutants of VPg reveal new cytopathology determinants in a picornavirus.Arias Esteban, ArmandoPerales, CeliaEscarmís, CristinaDomingo, EstebanPicornavirusBackground Success of a viral infection requires that each infected cell delivers a sufficient number of infectious particles to allow new rounds of infection. In picornaviruses, viral replication is initiated by the viral polymerase and a viral-coded protein, termed VPg, that primes RNA synthesis. Foot-and-mouth disease virus (FMDV) is exceptional among picornaviruses in that its genome encodes 3 copies of VPg. Why FMDV encodes three VPgs is unknown. Methodology and Principal Findings We have constructed four mutant FMDVs that encode only one VPg: either VPg1, VPg3, or two chimeric versions containing part of VPg1 and VPg3. All mutants, except that encoding only VPg1, were replication-competent. Unexpectedly, despite being replication-competent, the mutants did not form plaques on BHK-21 cell monolayers. The one-VPg mutant FMDVs released lower amounts of encapsidated viral RNA to the extracellular environment than wild type FMDV, suggesting that deficient plaque formation was associated with insufficient release of infectious progeny. Mutant FMDVs subjected to serial passages in BHK-21 cells regained plaque-forming capacity without modification of the number of copies of VPg. Substitutions in non-structural proteins 2C, 3A and VPg were associated with restoration of plaque formation. Specifically, replacement R55W in 2C was repeatedly found in several mutant viruses that had regained competence in plaque development. The effect of R55W in 2C was to mediate an increase in the extracellular viral RNA release without a detectable increase of total viral RNA that correlated with an enhanced capacity to alter and detach BHK-21 cells from the monolayer, the first stage of cell killing. Conclusions The results link the VPg copies in the FMDV genome with the cytopathology capacity of the virus, and have unveiled yet another function of 2C: modulation of picornavirus cell-to-cell transmission. Implications for picornaviruses pathogenesis are discussed.PLOS202620262010info:eu-repo/semantics/articleapplication/pdfapplication/pdfhttps://hdl.handle.net/10578/46900reponame:RUIdeRA. Repositorio Institucional de la UCLMinstname:Universidad de Castilla-La ManchaInglésBFU2008-02816/BMCBFU2008-02816/BMCinfo:eu-repo/semantics/openAccessoai:ruidera.uclm.es:10578/469002026-05-27T07:36:41Z
dc.title.none.fl_str_mv Deletion mutants of VPg reveal new cytopathology determinants in a picornavirus.
title Deletion mutants of VPg reveal new cytopathology determinants in a picornavirus.
spellingShingle Deletion mutants of VPg reveal new cytopathology determinants in a picornavirus.
Arias Esteban, Armando
Picornavirus
title_short Deletion mutants of VPg reveal new cytopathology determinants in a picornavirus.
title_full Deletion mutants of VPg reveal new cytopathology determinants in a picornavirus.
title_fullStr Deletion mutants of VPg reveal new cytopathology determinants in a picornavirus.
title_full_unstemmed Deletion mutants of VPg reveal new cytopathology determinants in a picornavirus.
title_sort Deletion mutants of VPg reveal new cytopathology determinants in a picornavirus.
dc.creator.none.fl_str_mv Arias Esteban, Armando
Perales, Celia
Escarmís, Cristina
Domingo, Esteban
author Arias Esteban, Armando
author_facet Arias Esteban, Armando
Perales, Celia
Escarmís, Cristina
Domingo, Esteban
author_role author
author2 Perales, Celia
Escarmís, Cristina
Domingo, Esteban
author2_role author
author
author
dc.subject.none.fl_str_mv Picornavirus
topic Picornavirus
description Background Success of a viral infection requires that each infected cell delivers a sufficient number of infectious particles to allow new rounds of infection. In picornaviruses, viral replication is initiated by the viral polymerase and a viral-coded protein, termed VPg, that primes RNA synthesis. Foot-and-mouth disease virus (FMDV) is exceptional among picornaviruses in that its genome encodes 3 copies of VPg. Why FMDV encodes three VPgs is unknown. Methodology and Principal Findings We have constructed four mutant FMDVs that encode only one VPg: either VPg1, VPg3, or two chimeric versions containing part of VPg1 and VPg3. All mutants, except that encoding only VPg1, were replication-competent. Unexpectedly, despite being replication-competent, the mutants did not form plaques on BHK-21 cell monolayers. The one-VPg mutant FMDVs released lower amounts of encapsidated viral RNA to the extracellular environment than wild type FMDV, suggesting that deficient plaque formation was associated with insufficient release of infectious progeny. Mutant FMDVs subjected to serial passages in BHK-21 cells regained plaque-forming capacity without modification of the number of copies of VPg. Substitutions in non-structural proteins 2C, 3A and VPg were associated with restoration of plaque formation. Specifically, replacement R55W in 2C was repeatedly found in several mutant viruses that had regained competence in plaque development. The effect of R55W in 2C was to mediate an increase in the extracellular viral RNA release without a detectable increase of total viral RNA that correlated with an enhanced capacity to alter and detach BHK-21 cells from the monolayer, the first stage of cell killing. Conclusions The results link the VPg copies in the FMDV genome with the cytopathology capacity of the virus, and have unveiled yet another function of 2C: modulation of picornavirus cell-to-cell transmission. Implications for picornaviruses pathogenesis are discussed.
publishDate 2010
dc.date.none.fl_str_mv 2010
2026
2026
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format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/10578/46900
url https://hdl.handle.net/10578/46900
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv BFU2008-02816/BMC
BFU2008-02816/BMC
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv PLOS
publisher.none.fl_str_mv PLOS
dc.source.none.fl_str_mv reponame:RUIdeRA. Repositorio Institucional de la UCLM
instname:Universidad de Castilla-La Mancha
instname_str Universidad de Castilla-La Mancha
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