An antiviral disulfide compound blocks interaction between arenavirus Z protein and cellular promyelocytic leukemia protein

Autores
Garcia, Cybele; Topisirovic, I.; Djavani, M.; Borden, K. L. B.; Damonte, Elsa Beatriz; Salvato, M. S.
Año de publicación
2010
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The promyelocytic leukemia protein (PML) forms nuclear bodies (NB) that can be redistributed by virus infection. In particular, lymphocytic choriomeningitis virus (LCMV) influences disruption of PML NB through the interaction of PML with the arenaviral Z protein. In a previous report, we have shown that the disulfide compound NSC20625 has antiviral and virucidal properties against arenaviruses, inducing unfolding and oligomerization of Z without affecting cellular RING-containing proteins such as the PML. Here, we further studied the effect of the zinc-finger-reactive disulfide NSC20625 on PML-Z interaction. In HepG2 cells infected with LCMV or transiently transfected with Z protein constructs, treatment with NSC20625 restored PML distribution from a diffuse-cytoplasmic pattern to punctate, discrete NB which appeared identical to NB found in control, uninfected cells. Similar results were obtained in cells transfected with a construct expressing a Z mutant in zinc-binding site 2 of the RING domain, confirming that this Z-PML interaction requires the integrity of only one zinc-binding site. Altogether, these results show that the compound NSC20625 suppressed Z-mediated PML NB disruption and may be used as a tool for designing novel antiviral strategies against arenavirus infection. © 2010 Elsevier Inc. All rights reserved.
Fil: Garcia, Cybele. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; Argentina
Fil: Topisirovic, I.. University of Montreal; Canadá
Fil: Djavani, M.. University of Maryland; Estados Unidos
Fil: Borden, K. L. B.. University of Montreal; Canadá
Fil: Damonte, Elsa Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; Argentina
Fil: Salvato, M. S.. University of Maryland; Estados Unidos
Materia
Antiviral Disulfide Agent
Arenavirus
Lymphocytic Choriomeningitis Virus
Promyelocytic Leukemia Protein
Ring-Finger Interactions
Z Protein
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:11336/66380
Acceder
id CONICETDig_b96c6d6f8f1f0ed41b4a02f87f3568d2
oai_identifier_str oai:ri.conicet.gov.ar:11336/66380
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling An antiviral disulfide compound blocks interaction between arenavirus Z protein and cellular promyelocytic leukemia proteinGarcia, CybeleTopisirovic, I.Djavani, M.Borden, K. L. B.Damonte, Elsa BeatrizSalvato, M. S.Antiviral Disulfide AgentArenavirusLymphocytic Choriomeningitis VirusPromyelocytic Leukemia ProteinRing-Finger InteractionsZ Proteinhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3The promyelocytic leukemia protein (PML) forms nuclear bodies (NB) that can be redistributed by virus infection. In particular, lymphocytic choriomeningitis virus (LCMV) influences disruption of PML NB through the interaction of PML with the arenaviral Z protein. In a previous report, we have shown that the disulfide compound NSC20625 has antiviral and virucidal properties against arenaviruses, inducing unfolding and oligomerization of Z without affecting cellular RING-containing proteins such as the PML. Here, we further studied the effect of the zinc-finger-reactive disulfide NSC20625 on PML-Z interaction. In HepG2 cells infected with LCMV or transiently transfected with Z protein constructs, treatment with NSC20625 restored PML distribution from a diffuse-cytoplasmic pattern to punctate, discrete NB which appeared identical to NB found in control, uninfected cells. Similar results were obtained in cells transfected with a construct expressing a Z mutant in zinc-binding site 2 of the RING domain, confirming that this Z-PML interaction requires the integrity of only one zinc-binding site. Altogether, these results show that the compound NSC20625 suppressed Z-mediated PML NB disruption and may be used as a tool for designing novel antiviral strategies against arenavirus infection. © 2010 Elsevier Inc. All rights reserved.Fil: Garcia, Cybele. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; ArgentinaFil: Topisirovic, I.. University of Montreal; CanadáFil: Djavani, M.. University of Maryland; Estados UnidosFil: Borden, K. L. B.. University of Montreal; CanadáFil: Damonte, Elsa Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; ArgentinaFil: Salvato, M. S.. University of Maryland; Estados UnidosAcademic Press Inc Elsevier Science2010-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/66380Garcia, Cybele; Topisirovic, I.; Djavani, M.; Borden, K. L. B.; Damonte, Elsa Beatriz; et al.; An antiviral disulfide compound blocks interaction between arenavirus Z protein and cellular promyelocytic leukemia protein; Academic Press Inc Elsevier Science; Biochemical and Biophysical Research Communications; 393; 4; 3-2010; 625-6300006-291XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0006291X10002512info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bbrc.2010.02.040info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:44:14Zoai:ri.conicet.gov.ar:11336/66380instacron: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:34982025-09-03 09:44:15.235CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv An antiviral disulfide compound blocks interaction between arenavirus Z protein and cellular promyelocytic leukemia protein
title An antiviral disulfide compound blocks interaction between arenavirus Z protein and cellular promyelocytic leukemia protein
spellingShingle An antiviral disulfide compound blocks interaction between arenavirus Z protein and cellular promyelocytic leukemia protein
Garcia, Cybele
Antiviral Disulfide Agent
Arenavirus
Lymphocytic Choriomeningitis Virus
Promyelocytic Leukemia Protein
Ring-Finger Interactions
Z Protein
title_short An antiviral disulfide compound blocks interaction between arenavirus Z protein and cellular promyelocytic leukemia protein
title_full An antiviral disulfide compound blocks interaction between arenavirus Z protein and cellular promyelocytic leukemia protein
title_fullStr An antiviral disulfide compound blocks interaction between arenavirus Z protein and cellular promyelocytic leukemia protein
title_full_unstemmed An antiviral disulfide compound blocks interaction between arenavirus Z protein and cellular promyelocytic leukemia protein
title_sort An antiviral disulfide compound blocks interaction between arenavirus Z protein and cellular promyelocytic leukemia protein
dc.creator.none.fl_str_mv Garcia, Cybele
Topisirovic, I.
Djavani, M.
Borden, K. L. B.
Damonte, Elsa Beatriz
Salvato, M. S.
author Garcia, Cybele
author_facet Garcia, Cybele
Topisirovic, I.
Djavani, M.
Borden, K. L. B.
Damonte, Elsa Beatriz
Salvato, M. S.
author_role author
author2 Topisirovic, I.
Djavani, M.
Borden, K. L. B.
Damonte, Elsa Beatriz
Salvato, M. S.
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Antiviral Disulfide Agent
Arenavirus
Lymphocytic Choriomeningitis Virus
Promyelocytic Leukemia Protein
Ring-Finger Interactions
Z Protein
topic Antiviral Disulfide Agent
Arenavirus
Lymphocytic Choriomeningitis Virus
Promyelocytic Leukemia Protein
Ring-Finger Interactions
Z Protein
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The promyelocytic leukemia protein (PML) forms nuclear bodies (NB) that can be redistributed by virus infection. In particular, lymphocytic choriomeningitis virus (LCMV) influences disruption of PML NB through the interaction of PML with the arenaviral Z protein. In a previous report, we have shown that the disulfide compound NSC20625 has antiviral and virucidal properties against arenaviruses, inducing unfolding and oligomerization of Z without affecting cellular RING-containing proteins such as the PML. Here, we further studied the effect of the zinc-finger-reactive disulfide NSC20625 on PML-Z interaction. In HepG2 cells infected with LCMV or transiently transfected with Z protein constructs, treatment with NSC20625 restored PML distribution from a diffuse-cytoplasmic pattern to punctate, discrete NB which appeared identical to NB found in control, uninfected cells. Similar results were obtained in cells transfected with a construct expressing a Z mutant in zinc-binding site 2 of the RING domain, confirming that this Z-PML interaction requires the integrity of only one zinc-binding site. Altogether, these results show that the compound NSC20625 suppressed Z-mediated PML NB disruption and may be used as a tool for designing novel antiviral strategies against arenavirus infection. © 2010 Elsevier Inc. All rights reserved.
Fil: Garcia, Cybele. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; Argentina
Fil: Topisirovic, I.. University of Montreal; Canadá
Fil: Djavani, M.. University of Maryland; Estados Unidos
Fil: Borden, K. L. B.. University of Montreal; Canadá
Fil: Damonte, Elsa Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; Argentina
Fil: Salvato, M. S.. University of Maryland; Estados Unidos
description The promyelocytic leukemia protein (PML) forms nuclear bodies (NB) that can be redistributed by virus infection. In particular, lymphocytic choriomeningitis virus (LCMV) influences disruption of PML NB through the interaction of PML with the arenaviral Z protein. In a previous report, we have shown that the disulfide compound NSC20625 has antiviral and virucidal properties against arenaviruses, inducing unfolding and oligomerization of Z without affecting cellular RING-containing proteins such as the PML. Here, we further studied the effect of the zinc-finger-reactive disulfide NSC20625 on PML-Z interaction. In HepG2 cells infected with LCMV or transiently transfected with Z protein constructs, treatment with NSC20625 restored PML distribution from a diffuse-cytoplasmic pattern to punctate, discrete NB which appeared identical to NB found in control, uninfected cells. Similar results were obtained in cells transfected with a construct expressing a Z mutant in zinc-binding site 2 of the RING domain, confirming that this Z-PML interaction requires the integrity of only one zinc-binding site. Altogether, these results show that the compound NSC20625 suppressed Z-mediated PML NB disruption and may be used as a tool for designing novel antiviral strategies against arenavirus infection. © 2010 Elsevier Inc. All rights reserved.
publishDate 2010
dc.date.none.fl_str_mv 2010-03
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/66380
Garcia, Cybele; Topisirovic, I.; Djavani, M.; Borden, K. L. B.; Damonte, Elsa Beatriz; et al.; An antiviral disulfide compound blocks interaction between arenavirus Z protein and cellular promyelocytic leukemia protein; Academic Press Inc Elsevier Science; Biochemical and Biophysical Research Communications; 393; 4; 3-2010; 625-630
0006-291X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/66380
identifier_str_mv Garcia, Cybele; Topisirovic, I.; Djavani, M.; Borden, K. L. B.; Damonte, Elsa Beatriz; et al.; An antiviral disulfide compound blocks interaction between arenavirus Z protein and cellular promyelocytic leukemia protein; Academic Press Inc Elsevier Science; Biochemical and Biophysical Research Communications; 393; 4; 3-2010; 625-630
0006-291X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0006291X10002512
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bbrc.2010.02.040
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
application/pdf
dc.publisher.none.fl_str_mv Academic Press Inc Elsevier Science
publisher.none.fl_str_mv Academic Press Inc Elsevier Science
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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score 13.13397

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