DDX3 suppresses type I interferons and favors viral replication during Arenavirus infection

Autores
Loureiro, Maria Eugenia; Zorzetto Fernandes, Andre Luiz; Radoshitzky, Sheli; Chi, Xiaoli; Dallari, Simone; Marooki, Nuha; Lèger, Psylvia; Foscaldi, Sabrina Andrea; Harjono, Vince; Sharma, Sonia; Zid, Brian M.; Lopez, Nora Mabel; de la Torre, Juan Carlos; Bavari, Sina; Zuniga, Elina Isabel
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Several arenaviruses cause hemorrhagic fever (HF) diseases that are associated with high morbidity and mortality in humans. Accordingly, HF arenaviruses have been listed as top-priority emerging diseases for which countermeasures are urgently needed. Because arenavirus nucleoprotein (NP) plays critical roles in both virus multiplication and immune-evasion, we used an unbiased proteomic approach to identify NP-interacting proteins in human cells. DDX3, a DEAD-box ATP-dependent-RNA-helicase, interacted with NP in both NP-transfected and virus-infected cells. Importantly, DDX3 deficiency compromised the propagation of both Old and New World arenaviruses, including the HF arenaviruses Lassa and Junin viruses. The DDX3 role in promoting arenavirus multiplication associated with both a previously un-recognized DDX3 inhibitory role in type I interferon production in arenavirus infected cells and a positive DDX3 effect on arenavirus RNA synthesis that was dependent on its ATPase and Helicase activities. Our results uncover novel mechanisms used by arenaviruses to exploit the host machinery and subvert immunity, singling out DDX3 as a potential host target for developing new therapies against highly pathogenic arenaviruses.
Fil: Loureiro, Maria Eugenia. University of California at San Diego; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Zorzetto Fernandes, Andre Luiz. University of California at San Diego; Estados Unidos
Fil: Radoshitzky, Sheli. United States Army Medical Research Institute of Infectious Diseases; Estados Unidos
Fil: Chi, Xiaoli. United States Army Medical Research Institute of Infectious Diseases; Estados Unidos
Fil: Dallari, Simone. University of California at San Diego; Estados Unidos
Fil: Marooki, Nuha. University of California at San Diego; Estados Unidos
Fil: Lèger, Psylvia. University of California at San Diego; Estados Unidos
Fil: Foscaldi, Sabrina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología "Dr. César Milstein". Fundación Pablo Cassará. Instituto de Ciencia y Tecnología "Dr. César Milstein"; Argentina
Fil: Harjono, Vince. University of California at San Diego; Estados Unidos
Fil: Sharma, Sonia. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Zid, Brian M.. University of California at San Diego; Estados Unidos
Fil: Lopez, Nora Mabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología "Dr. César Milstein". Fundación Pablo Cassará. Instituto de Ciencia y Tecnología "Dr. César Milstein"; Argentina. Ministerio de Producción y Trabajo. Secretaría de Gobierno de Agroindustria. Servicio Nacional de Sanidad y Calidad Agroalimentaria. Centro de Virología Humana y Animal. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Virología Humana y Animal; Argentina
Fil: de la Torre, Juan Carlos. The Scripps Research Institute; Estados Unidos
Fil: Bavari, Sina. United States Army Medical Research Institute of Infectious Diseases; Estados Unidos
Fil: Zuniga, Elina Isabel. University of California at San Diego; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
ARENAVIRUS
DDX3
REPLICATION
INTERFERON
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:11336/97302
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/97302
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling DDX3 suppresses type I interferons and favors viral replication during Arenavirus infectionLoureiro, Maria EugeniaZorzetto Fernandes, Andre LuizRadoshitzky, SheliChi, XiaoliDallari, SimoneMarooki, NuhaLèger, PsylviaFoscaldi, Sabrina AndreaHarjono, VinceSharma, SoniaZid, Brian M.Lopez, Nora Mabelde la Torre, Juan CarlosBavari, SinaZuniga, Elina IsabelARENAVIRUSDDX3REPLICATIONINTERFERONhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Several arenaviruses cause hemorrhagic fever (HF) diseases that are associated with high morbidity and mortality in humans. Accordingly, HF arenaviruses have been listed as top-priority emerging diseases for which countermeasures are urgently needed. Because arenavirus nucleoprotein (NP) plays critical roles in both virus multiplication and immune-evasion, we used an unbiased proteomic approach to identify NP-interacting proteins in human cells. DDX3, a DEAD-box ATP-dependent-RNA-helicase, interacted with NP in both NP-transfected and virus-infected cells. Importantly, DDX3 deficiency compromised the propagation of both Old and New World arenaviruses, including the HF arenaviruses Lassa and Junin viruses. The DDX3 role in promoting arenavirus multiplication associated with both a previously un-recognized DDX3 inhibitory role in type I interferon production in arenavirus infected cells and a positive DDX3 effect on arenavirus RNA synthesis that was dependent on its ATPase and Helicase activities. Our results uncover novel mechanisms used by arenaviruses to exploit the host machinery and subvert immunity, singling out DDX3 as a potential host target for developing new therapies against highly pathogenic arenaviruses.Fil: Loureiro, Maria Eugenia. University of California at San Diego; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Zorzetto Fernandes, Andre Luiz. University of California at San Diego; Estados UnidosFil: Radoshitzky, Sheli. United States Army Medical Research Institute of Infectious Diseases; Estados UnidosFil: Chi, Xiaoli. United States Army Medical Research Institute of Infectious Diseases; Estados UnidosFil: Dallari, Simone. University of California at San Diego; Estados UnidosFil: Marooki, Nuha. University of California at San Diego; Estados UnidosFil: Lèger, Psylvia. University of California at San Diego; Estados UnidosFil: Foscaldi, Sabrina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología "Dr. César Milstein". Fundación Pablo Cassará. Instituto de Ciencia y Tecnología "Dr. César Milstein"; ArgentinaFil: Harjono, Vince. University of California at San Diego; Estados UnidosFil: Sharma, Sonia. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Zid, Brian M.. University of California at San Diego; Estados UnidosFil: Lopez, Nora Mabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología "Dr. César Milstein". Fundación Pablo Cassará. Instituto de Ciencia y Tecnología "Dr. César Milstein"; Argentina. Ministerio de Producción y Trabajo. Secretaría de Gobierno de Agroindustria. Servicio Nacional de Sanidad y Calidad Agroalimentaria. Centro de Virología Humana y Animal. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Virología Humana y Animal; ArgentinaFil: de la Torre, Juan Carlos. The Scripps Research Institute; Estados UnidosFil: Bavari, Sina. United States Army Medical Research Institute of Infectious Diseases; Estados UnidosFil: Zuniga, Elina Isabel. University of California at San Diego; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaPublic Library of Science2018-07info: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/11336/97302Loureiro, Maria Eugenia; Zorzetto Fernandes, Andre Luiz; Radoshitzky, Sheli; Chi, Xiaoli; Dallari, Simone; et al.; DDX3 suppresses type I interferons and favors viral replication during Arenavirus infection; Public Library of Science; Plos Pathogens; 14; 7; 7-2018; 1-28; e10071251553-7366CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1007125info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.ppat.1007125info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:35:49Zoai:ri.conicet.gov.ar:11336/97302instacron: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 09:35:49.386CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv DDX3 suppresses type I interferons and favors viral replication during Arenavirus infection
title DDX3 suppresses type I interferons and favors viral replication during Arenavirus infection
spellingShingle DDX3 suppresses type I interferons and favors viral replication during Arenavirus infection
Loureiro, Maria Eugenia
ARENAVIRUS
DDX3
REPLICATION
INTERFERON
title_short DDX3 suppresses type I interferons and favors viral replication during Arenavirus infection
title_full DDX3 suppresses type I interferons and favors viral replication during Arenavirus infection
title_fullStr DDX3 suppresses type I interferons and favors viral replication during Arenavirus infection
title_full_unstemmed DDX3 suppresses type I interferons and favors viral replication during Arenavirus infection
title_sort DDX3 suppresses type I interferons and favors viral replication during Arenavirus infection
dc.creator.none.fl_str_mv Loureiro, Maria Eugenia
Zorzetto Fernandes, Andre Luiz
Radoshitzky, Sheli
Chi, Xiaoli
Dallari, Simone
Marooki, Nuha
Lèger, Psylvia
Foscaldi, Sabrina Andrea
Harjono, Vince
Sharma, Sonia
Zid, Brian M.
Lopez, Nora Mabel
de la Torre, Juan Carlos
Bavari, Sina
Zuniga, Elina Isabel
author Loureiro, Maria Eugenia
author_facet Loureiro, Maria Eugenia
Zorzetto Fernandes, Andre Luiz
Radoshitzky, Sheli
Chi, Xiaoli
Dallari, Simone
Marooki, Nuha
Lèger, Psylvia
Foscaldi, Sabrina Andrea
Harjono, Vince
Sharma, Sonia
Zid, Brian M.
Lopez, Nora Mabel
de la Torre, Juan Carlos
Bavari, Sina
Zuniga, Elina Isabel
author_role author
author2 Zorzetto Fernandes, Andre Luiz
Radoshitzky, Sheli
Chi, Xiaoli
Dallari, Simone
Marooki, Nuha
Lèger, Psylvia
Foscaldi, Sabrina Andrea
Harjono, Vince
Sharma, Sonia
Zid, Brian M.
Lopez, Nora Mabel
de la Torre, Juan Carlos
Bavari, Sina
Zuniga, Elina Isabel
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ARENAVIRUS
DDX3
REPLICATION
INTERFERON
topic ARENAVIRUS
DDX3
REPLICATION
INTERFERON
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Several arenaviruses cause hemorrhagic fever (HF) diseases that are associated with high morbidity and mortality in humans. Accordingly, HF arenaviruses have been listed as top-priority emerging diseases for which countermeasures are urgently needed. Because arenavirus nucleoprotein (NP) plays critical roles in both virus multiplication and immune-evasion, we used an unbiased proteomic approach to identify NP-interacting proteins in human cells. DDX3, a DEAD-box ATP-dependent-RNA-helicase, interacted with NP in both NP-transfected and virus-infected cells. Importantly, DDX3 deficiency compromised the propagation of both Old and New World arenaviruses, including the HF arenaviruses Lassa and Junin viruses. The DDX3 role in promoting arenavirus multiplication associated with both a previously un-recognized DDX3 inhibitory role in type I interferon production in arenavirus infected cells and a positive DDX3 effect on arenavirus RNA synthesis that was dependent on its ATPase and Helicase activities. Our results uncover novel mechanisms used by arenaviruses to exploit the host machinery and subvert immunity, singling out DDX3 as a potential host target for developing new therapies against highly pathogenic arenaviruses.
Fil: Loureiro, Maria Eugenia. University of California at San Diego; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Zorzetto Fernandes, Andre Luiz. University of California at San Diego; Estados Unidos
Fil: Radoshitzky, Sheli. United States Army Medical Research Institute of Infectious Diseases; Estados Unidos
Fil: Chi, Xiaoli. United States Army Medical Research Institute of Infectious Diseases; Estados Unidos
Fil: Dallari, Simone. University of California at San Diego; Estados Unidos
Fil: Marooki, Nuha. University of California at San Diego; Estados Unidos
Fil: Lèger, Psylvia. University of California at San Diego; Estados Unidos
Fil: Foscaldi, Sabrina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología "Dr. César Milstein". Fundación Pablo Cassará. Instituto de Ciencia y Tecnología "Dr. César Milstein"; Argentina
Fil: Harjono, Vince. University of California at San Diego; Estados Unidos
Fil: Sharma, Sonia. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Zid, Brian M.. University of California at San Diego; Estados Unidos
Fil: Lopez, Nora Mabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología "Dr. César Milstein". Fundación Pablo Cassará. Instituto de Ciencia y Tecnología "Dr. César Milstein"; Argentina. Ministerio de Producción y Trabajo. Secretaría de Gobierno de Agroindustria. Servicio Nacional de Sanidad y Calidad Agroalimentaria. Centro de Virología Humana y Animal. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Virología Humana y Animal; Argentina
Fil: de la Torre, Juan Carlos. The Scripps Research Institute; Estados Unidos
Fil: Bavari, Sina. United States Army Medical Research Institute of Infectious Diseases; Estados Unidos
Fil: Zuniga, Elina Isabel. University of California at San Diego; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Several arenaviruses cause hemorrhagic fever (HF) diseases that are associated with high morbidity and mortality in humans. Accordingly, HF arenaviruses have been listed as top-priority emerging diseases for which countermeasures are urgently needed. Because arenavirus nucleoprotein (NP) plays critical roles in both virus multiplication and immune-evasion, we used an unbiased proteomic approach to identify NP-interacting proteins in human cells. DDX3, a DEAD-box ATP-dependent-RNA-helicase, interacted with NP in both NP-transfected and virus-infected cells. Importantly, DDX3 deficiency compromised the propagation of both Old and New World arenaviruses, including the HF arenaviruses Lassa and Junin viruses. The DDX3 role in promoting arenavirus multiplication associated with both a previously un-recognized DDX3 inhibitory role in type I interferon production in arenavirus infected cells and a positive DDX3 effect on arenavirus RNA synthesis that was dependent on its ATPase and Helicase activities. Our results uncover novel mechanisms used by arenaviruses to exploit the host machinery and subvert immunity, singling out DDX3 as a potential host target for developing new therapies against highly pathogenic arenaviruses.
publishDate 2018
dc.date.none.fl_str_mv 2018-07
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/11336/97302
Loureiro, Maria Eugenia; Zorzetto Fernandes, Andre Luiz; Radoshitzky, Sheli; Chi, Xiaoli; Dallari, Simone; et al.; DDX3 suppresses type I interferons and favors viral replication during Arenavirus infection; Public Library of Science; Plos Pathogens; 14; 7; 7-2018; 1-28; e1007125
1553-7366
CONICET Digital
CONICET
url http://hdl.handle.net/11336/97302
identifier_str_mv Loureiro, Maria Eugenia; Zorzetto Fernandes, Andre Luiz; Radoshitzky, Sheli; Chi, Xiaoli; Dallari, Simone; et al.; DDX3 suppresses type I interferons and favors viral replication during Arenavirus infection; Public Library of Science; Plos Pathogens; 14; 7; 7-2018; 1-28; e1007125
1553-7366
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1007125
info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.ppat.1007125
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 Public Library of Science
publisher.none.fl_str_mv Public Library of 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 13.070432

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