HIV-1 BF intersubtype recombinant Vpu second alpha helix plays an important role in the viral release and BST-2 degradation

Autores
de Candia, Cristian Ariel; Espada, Constanza Eleonora; Duette, Gabriel; Salomon, Horacio Eduardo; Carobene, Mauricio
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
We previously reported a naturally occurring BF intersubtype recombinant Vpu variant with augmented capacity to enhance viral replication. Structural analysis of this variant revealed that its transmembrane domain (TMD) and α-helix I in the cytoplasmic domain (CTD) corresponded to subtype B, whereas CTD α-helix II corresponded to subtype F1. This work was aimed at evaluating the role of Vpu CTD α-helix II domain on viral release enhancement and down-modulation of BST-2 and CD4 from cell surface. In addition, as serine residues in either Vpu amino acid positions 61 or 64 have been shown to regulate Vpu intracellular half-life, which in turn could influence the magnitude of viral release, we also studied the impact of these residues in the BF Vpu functions, since S61 and S64 are infrequently found among BF recombinant Vpu variants. Our results showed that interchange of Vpu α-helix II between subtypes (B→F) directly correlated with enhancement of viral release and, to a lesser extent, with changes in the capacity to down-modulate BST-2 and CD4 of the resulting chimera. No statistical differences on viral release and BST-2 down-modulation were observed between Vpu BF and VpuBF E61S. On the other hand, VpuBF A64S showed a slightly reduced capacity to enhance viral production but was modestly more efficient than VpuBF in down-modulating BST-2. In summary, our observations clearly evidence that α-helix II is actively involved in Vpu viral release-promoting activity, and that intersubtype recombination between subtypes B and F1 originated a protein variant with higher potential to boost the spread of the recombinant strain that harbors it.
Fil: de Candia, Cristian Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina;
Fil: Espada, Constanza Eleonora. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiologia. Centro Nacional de Referencia del Sida; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina;
Fil: Duette, Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina; Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología; Argentina;
Fil: Salomon, Horacio Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina; Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología; Argentina;
Fil: Carobene, Mauricio. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiologia. Centro Nacional de Referencia del Sida; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina;
Materia
HIV-1
Vpu
Recombination
Viral release
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/1808

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oai_identifier_str oai:ri.conicet.gov.ar:11336/1808
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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling HIV-1 BF intersubtype recombinant Vpu second alpha helix plays an important role in the viral release and BST-2 degradationde Candia, Cristian ArielEspada, Constanza EleonoraDuette, GabrielSalomon, Horacio EduardoCarobene, MauricioHIV-1VpuRecombinationViral releasehttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1We previously reported a naturally occurring BF intersubtype recombinant Vpu variant with augmented capacity to enhance viral replication. Structural analysis of this variant revealed that its transmembrane domain (TMD) and α-helix I in the cytoplasmic domain (CTD) corresponded to subtype B, whereas CTD α-helix II corresponded to subtype F1. This work was aimed at evaluating the role of Vpu CTD α-helix II domain on viral release enhancement and down-modulation of BST-2 and CD4 from cell surface. In addition, as serine residues in either Vpu amino acid positions 61 or 64 have been shown to regulate Vpu intracellular half-life, which in turn could influence the magnitude of viral release, we also studied the impact of these residues in the BF Vpu functions, since S61 and S64 are infrequently found among BF recombinant Vpu variants. Our results showed that interchange of Vpu α-helix II between subtypes (B→F) directly correlated with enhancement of viral release and, to a lesser extent, with changes in the capacity to down-modulate BST-2 and CD4 of the resulting chimera. No statistical differences on viral release and BST-2 down-modulation were observed between Vpu BF and VpuBF E61S. On the other hand, VpuBF A64S showed a slightly reduced capacity to enhance viral production but was modestly more efficient than VpuBF in down-modulating BST-2. In summary, our observations clearly evidence that α-helix II is actively involved in Vpu viral release-promoting activity, and that intersubtype recombination between subtypes B and F1 originated a protein variant with higher potential to boost the spread of the recombinant strain that harbors it.Fil: de Candia, Cristian Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina;Fil: Espada, Constanza Eleonora. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiologia. Centro Nacional de Referencia del Sida; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina;Fil: Duette, Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina; Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología; Argentina;Fil: Salomon, Horacio Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina; Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología; Argentina;Fil: Carobene, Mauricio. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiologia. Centro Nacional de Referencia del Sida; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina;Society for General Microbiology2013-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/1808de Candia, Cristian Ariel; Espada, Constanza Eleonora; Duette, Gabriel; Salomon, Horacio Eduardo; Carobene, Mauricio; HIV-1 BF intersubtype recombinant Vpu second alpha helix plays an important role in the viral release and BST-2 degradation; Society for General Microbiology; Journal of General Virology; 94; 4-2013; 758-7660022-1317enginfo:eu-repo/semantics/altIdentifier/doi/doi:10.1099/vir.0.047746-0info:eu-repo/semantics/altIdentifier/url/http://jgv.sgmjournals.org/content/journal/jgv/10.1099/vir.0.047746-0?crawler=true&mimetype=application/pdfinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:43:13Zoai:ri.conicet.gov.ar:11336/1808instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:43:13.824CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv HIV-1 BF intersubtype recombinant Vpu second alpha helix plays an important role in the viral release and BST-2 degradation
title HIV-1 BF intersubtype recombinant Vpu second alpha helix plays an important role in the viral release and BST-2 degradation
spellingShingle HIV-1 BF intersubtype recombinant Vpu second alpha helix plays an important role in the viral release and BST-2 degradation
de Candia, Cristian Ariel
HIV-1
Vpu
Recombination
Viral release
title_short HIV-1 BF intersubtype recombinant Vpu second alpha helix plays an important role in the viral release and BST-2 degradation
title_full HIV-1 BF intersubtype recombinant Vpu second alpha helix plays an important role in the viral release and BST-2 degradation
title_fullStr HIV-1 BF intersubtype recombinant Vpu second alpha helix plays an important role in the viral release and BST-2 degradation
title_full_unstemmed HIV-1 BF intersubtype recombinant Vpu second alpha helix plays an important role in the viral release and BST-2 degradation
title_sort HIV-1 BF intersubtype recombinant Vpu second alpha helix plays an important role in the viral release and BST-2 degradation
dc.creator.none.fl_str_mv de Candia, Cristian Ariel
Espada, Constanza Eleonora
Duette, Gabriel
Salomon, Horacio Eduardo
Carobene, Mauricio
author de Candia, Cristian Ariel
author_facet de Candia, Cristian Ariel
Espada, Constanza Eleonora
Duette, Gabriel
Salomon, Horacio Eduardo
Carobene, Mauricio
author_role author
author2 Espada, Constanza Eleonora
Duette, Gabriel
Salomon, Horacio Eduardo
Carobene, Mauricio
author2_role author
author
author
author
dc.subject.none.fl_str_mv HIV-1
Vpu
Recombination
Viral release
topic HIV-1
Vpu
Recombination
Viral release
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv We previously reported a naturally occurring BF intersubtype recombinant Vpu variant with augmented capacity to enhance viral replication. Structural analysis of this variant revealed that its transmembrane domain (TMD) and α-helix I in the cytoplasmic domain (CTD) corresponded to subtype B, whereas CTD α-helix II corresponded to subtype F1. This work was aimed at evaluating the role of Vpu CTD α-helix II domain on viral release enhancement and down-modulation of BST-2 and CD4 from cell surface. In addition, as serine residues in either Vpu amino acid positions 61 or 64 have been shown to regulate Vpu intracellular half-life, which in turn could influence the magnitude of viral release, we also studied the impact of these residues in the BF Vpu functions, since S61 and S64 are infrequently found among BF recombinant Vpu variants. Our results showed that interchange of Vpu α-helix II between subtypes (B→F) directly correlated with enhancement of viral release and, to a lesser extent, with changes in the capacity to down-modulate BST-2 and CD4 of the resulting chimera. No statistical differences on viral release and BST-2 down-modulation were observed between Vpu BF and VpuBF E61S. On the other hand, VpuBF A64S showed a slightly reduced capacity to enhance viral production but was modestly more efficient than VpuBF in down-modulating BST-2. In summary, our observations clearly evidence that α-helix II is actively involved in Vpu viral release-promoting activity, and that intersubtype recombination between subtypes B and F1 originated a protein variant with higher potential to boost the spread of the recombinant strain that harbors it.
Fil: de Candia, Cristian Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina;
Fil: Espada, Constanza Eleonora. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiologia. Centro Nacional de Referencia del Sida; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina;
Fil: Duette, Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina; Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología; Argentina;
Fil: Salomon, Horacio Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina; Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología; Argentina;
Fil: Carobene, Mauricio. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiologia. Centro Nacional de Referencia del Sida; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina;
description We previously reported a naturally occurring BF intersubtype recombinant Vpu variant with augmented capacity to enhance viral replication. Structural analysis of this variant revealed that its transmembrane domain (TMD) and α-helix I in the cytoplasmic domain (CTD) corresponded to subtype B, whereas CTD α-helix II corresponded to subtype F1. This work was aimed at evaluating the role of Vpu CTD α-helix II domain on viral release enhancement and down-modulation of BST-2 and CD4 from cell surface. In addition, as serine residues in either Vpu amino acid positions 61 or 64 have been shown to regulate Vpu intracellular half-life, which in turn could influence the magnitude of viral release, we also studied the impact of these residues in the BF Vpu functions, since S61 and S64 are infrequently found among BF recombinant Vpu variants. Our results showed that interchange of Vpu α-helix II between subtypes (B→F) directly correlated with enhancement of viral release and, to a lesser extent, with changes in the capacity to down-modulate BST-2 and CD4 of the resulting chimera. No statistical differences on viral release and BST-2 down-modulation were observed between Vpu BF and VpuBF E61S. On the other hand, VpuBF A64S showed a slightly reduced capacity to enhance viral production but was modestly more efficient than VpuBF in down-modulating BST-2. In summary, our observations clearly evidence that α-helix II is actively involved in Vpu viral release-promoting activity, and that intersubtype recombination between subtypes B and F1 originated a protein variant with higher potential to boost the spread of the recombinant strain that harbors it.
publishDate 2013
dc.date.none.fl_str_mv 2013-04
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
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info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/1808
de Candia, Cristian Ariel; Espada, Constanza Eleonora; Duette, Gabriel; Salomon, Horacio Eduardo; Carobene, Mauricio; HIV-1 BF intersubtype recombinant Vpu second alpha helix plays an important role in the viral release and BST-2 degradation; Society for General Microbiology; Journal of General Virology; 94; 4-2013; 758-766
0022-1317
url http://hdl.handle.net/11336/1808
identifier_str_mv de Candia, Cristian Ariel; Espada, Constanza Eleonora; Duette, Gabriel; Salomon, Horacio Eduardo; Carobene, Mauricio; HIV-1 BF intersubtype recombinant Vpu second alpha helix plays an important role in the viral release and BST-2 degradation; Society for General Microbiology; Journal of General Virology; 94; 4-2013; 758-766
0022-1317
dc.language.none.fl_str_mv eng
language eng
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dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Society for General Microbiology
publisher.none.fl_str_mv Society for General Microbiology
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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