Kaposi's sarcoma herpesvirus activates the hypoxia response to usurp HIF2α-dependent translation initiation for replication and oncogenesis

Autores
Méndez Solís, Omayra; Bendjennat, Mourad; Naipauer, Julian; Theodoridis, Phaedra R.; Ho, J.J. David; Verdun, Ramiro E.; Hare, Joshua M.; Cesarman, Ethel; Lee, Stephen; Mesri, Enrique Alfredo
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Kaposi's sarcoma herpesvirus (KSHV) is an angiogenesis-inducing oncovirus whose ability to usurp the oxygen-sensing machinery is central to its oncogenicity. By upregulating the hypoxia-inducible factors (HIFs), KSHV reprograms infected cells to a hypoxia-like state, triggering angiogenesis. Here we identify a link between KSHV replicative biology and oncogenicity by showing that KSHV's ability to regulate HIF2α levels and localization to the endoplasmic reticulum (ER) in normoxia enables translation of viral lytic mRNAs through the HIF2α-regulated eIF4E2 translation-initiation complex. This mechanism of translation in infected cells is critical for lytic protein synthesis and contributes to KSHV-induced PDGFRA activation and VEGF secretion. Thus, KSHV regulation of the oxygen-sensing machinery allows virally infected cells to initiate translation via the mTOR-dependent eIF4E1 or the HIF2α-dependent, mTOR-independent, eIF4E2. This “translation initiation plasticity” (TRIP) is an oncoviral strategy used to optimize viral protein expression that links molecular strategies of viral replication to angiogenicity and oncogenesis.
Fil: Méndez Solís, Omayra. University of Miami; Estados Unidos
Fil: Bendjennat, Mourad. University of Miami; Estados Unidos
Fil: Naipauer, Julian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina. University of Miami; Estados Unidos
Fil: Theodoridis, Phaedra R.. University of Miami; Estados Unidos
Fil: Ho, J.J. David. University of Miami; Estados Unidos
Fil: Verdun, Ramiro E.. University of Miami; Estados Unidos
Fil: Hare, Joshua M.. University of Miami; Estados Unidos
Fil: Cesarman, Ethel. Weill Cornell Medicine; Estados Unidos
Fil: Lee, Stephen. University of Miami; Estados Unidos
Fil: Mesri, Enrique Alfredo. University of Miami; Estados Unidos
Materia
EIF4E2 CAP BINDING
EPAS1
HHV-8
HYPOXIA-INDUCIBLE FACTORS
KAPOSI'S SARCOMA HERPESVIRUS
KSHV
OXYGEN-REGULATED TRANSLATION INITIATION
PDGFRA
VIRAL ONCOGENESIS
VIRAL REPLICATION
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/181803
Acceder
id CONICETDig_50220cffe2064947092eb8e15e8130a6
oai_identifier_str oai:ri.conicet.gov.ar:11336/181803
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Kaposi's sarcoma herpesvirus activates the hypoxia response to usurp HIF2α-dependent translation initiation for replication and oncogenesisMéndez Solís, OmayraBendjennat, MouradNaipauer, JulianTheodoridis, Phaedra R.Ho, J.J. DavidVerdun, Ramiro E.Hare, Joshua M.Cesarman, EthelLee, StephenMesri, Enrique AlfredoEIF4E2 CAP BINDINGEPAS1HHV-8HYPOXIA-INDUCIBLE FACTORSKAPOSI'S SARCOMA HERPESVIRUSKSHVOXYGEN-REGULATED TRANSLATION INITIATIONPDGFRAVIRAL ONCOGENESISVIRAL REPLICATIONhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Kaposi's sarcoma herpesvirus (KSHV) is an angiogenesis-inducing oncovirus whose ability to usurp the oxygen-sensing machinery is central to its oncogenicity. By upregulating the hypoxia-inducible factors (HIFs), KSHV reprograms infected cells to a hypoxia-like state, triggering angiogenesis. Here we identify a link between KSHV replicative biology and oncogenicity by showing that KSHV's ability to regulate HIF2α levels and localization to the endoplasmic reticulum (ER) in normoxia enables translation of viral lytic mRNAs through the HIF2α-regulated eIF4E2 translation-initiation complex. This mechanism of translation in infected cells is critical for lytic protein synthesis and contributes to KSHV-induced PDGFRA activation and VEGF secretion. Thus, KSHV regulation of the oxygen-sensing machinery allows virally infected cells to initiate translation via the mTOR-dependent eIF4E1 or the HIF2α-dependent, mTOR-independent, eIF4E2. This “translation initiation plasticity” (TRIP) is an oncoviral strategy used to optimize viral protein expression that links molecular strategies of viral replication to angiogenicity and oncogenesis.Fil: Méndez Solís, Omayra. University of Miami; Estados UnidosFil: Bendjennat, Mourad. University of Miami; Estados UnidosFil: Naipauer, Julian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina. University of Miami; Estados UnidosFil: Theodoridis, Phaedra R.. University of Miami; Estados UnidosFil: Ho, J.J. David. University of Miami; Estados UnidosFil: Verdun, Ramiro E.. University of Miami; Estados UnidosFil: Hare, Joshua M.. University of Miami; Estados UnidosFil: Cesarman, Ethel. Weill Cornell Medicine; Estados UnidosFil: Lee, Stephen. University of Miami; Estados UnidosFil: Mesri, Enrique Alfredo. University of Miami; Estados UnidosElsevier Science2021-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/181803Méndez Solís, Omayra; Bendjennat, Mourad; Naipauer, Julian; Theodoridis, Phaedra R.; Ho, J.J. David; et al.; Kaposi's sarcoma herpesvirus activates the hypoxia response to usurp HIF2α-dependent translation initiation for replication and oncogenesis; Elsevier Science; Cell Reports; 37; 13; 12-2021; 1-302211-1247CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S2211124721016405info:eu-repo/semantics/altIdentifier/doi/10.1016/j.celrep.2021.110144info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:55:34Zoai:ri.conicet.gov.ar:11336/181803instacron: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 09:55:34.634CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Kaposi's sarcoma herpesvirus activates the hypoxia response to usurp HIF2α-dependent translation initiation for replication and oncogenesis
title Kaposi's sarcoma herpesvirus activates the hypoxia response to usurp HIF2α-dependent translation initiation for replication and oncogenesis
spellingShingle Kaposi's sarcoma herpesvirus activates the hypoxia response to usurp HIF2α-dependent translation initiation for replication and oncogenesis
Méndez Solís, Omayra
EIF4E2 CAP BINDING
EPAS1
HHV-8
HYPOXIA-INDUCIBLE FACTORS
KAPOSI'S SARCOMA HERPESVIRUS
KSHV
OXYGEN-REGULATED TRANSLATION INITIATION
PDGFRA
VIRAL ONCOGENESIS
VIRAL REPLICATION
title_short Kaposi's sarcoma herpesvirus activates the hypoxia response to usurp HIF2α-dependent translation initiation for replication and oncogenesis
title_full Kaposi's sarcoma herpesvirus activates the hypoxia response to usurp HIF2α-dependent translation initiation for replication and oncogenesis
title_fullStr Kaposi's sarcoma herpesvirus activates the hypoxia response to usurp HIF2α-dependent translation initiation for replication and oncogenesis
title_full_unstemmed Kaposi's sarcoma herpesvirus activates the hypoxia response to usurp HIF2α-dependent translation initiation for replication and oncogenesis
title_sort Kaposi's sarcoma herpesvirus activates the hypoxia response to usurp HIF2α-dependent translation initiation for replication and oncogenesis
dc.creator.none.fl_str_mv Méndez Solís, Omayra
Bendjennat, Mourad
Naipauer, Julian
Theodoridis, Phaedra R.
Ho, J.J. David
Verdun, Ramiro E.
Hare, Joshua M.
Cesarman, Ethel
Lee, Stephen
Mesri, Enrique Alfredo
author Méndez Solís, Omayra
author_facet Méndez Solís, Omayra
Bendjennat, Mourad
Naipauer, Julian
Theodoridis, Phaedra R.
Ho, J.J. David
Verdun, Ramiro E.
Hare, Joshua M.
Cesarman, Ethel
Lee, Stephen
Mesri, Enrique Alfredo
author_role author
author2 Bendjennat, Mourad
Naipauer, Julian
Theodoridis, Phaedra R.
Ho, J.J. David
Verdun, Ramiro E.
Hare, Joshua M.
Cesarman, Ethel
Lee, Stephen
Mesri, Enrique Alfredo
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv EIF4E2 CAP BINDING
EPAS1
HHV-8
HYPOXIA-INDUCIBLE FACTORS
KAPOSI'S SARCOMA HERPESVIRUS
KSHV
OXYGEN-REGULATED TRANSLATION INITIATION
PDGFRA
VIRAL ONCOGENESIS
VIRAL REPLICATION
topic EIF4E2 CAP BINDING
EPAS1
HHV-8
HYPOXIA-INDUCIBLE FACTORS
KAPOSI'S SARCOMA HERPESVIRUS
KSHV
OXYGEN-REGULATED TRANSLATION INITIATION
PDGFRA
VIRAL ONCOGENESIS
VIRAL REPLICATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Kaposi's sarcoma herpesvirus (KSHV) is an angiogenesis-inducing oncovirus whose ability to usurp the oxygen-sensing machinery is central to its oncogenicity. By upregulating the hypoxia-inducible factors (HIFs), KSHV reprograms infected cells to a hypoxia-like state, triggering angiogenesis. Here we identify a link between KSHV replicative biology and oncogenicity by showing that KSHV's ability to regulate HIF2α levels and localization to the endoplasmic reticulum (ER) in normoxia enables translation of viral lytic mRNAs through the HIF2α-regulated eIF4E2 translation-initiation complex. This mechanism of translation in infected cells is critical for lytic protein synthesis and contributes to KSHV-induced PDGFRA activation and VEGF secretion. Thus, KSHV regulation of the oxygen-sensing machinery allows virally infected cells to initiate translation via the mTOR-dependent eIF4E1 or the HIF2α-dependent, mTOR-independent, eIF4E2. This “translation initiation plasticity” (TRIP) is an oncoviral strategy used to optimize viral protein expression that links molecular strategies of viral replication to angiogenicity and oncogenesis.
Fil: Méndez Solís, Omayra. University of Miami; Estados Unidos
Fil: Bendjennat, Mourad. University of Miami; Estados Unidos
Fil: Naipauer, Julian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina. University of Miami; Estados Unidos
Fil: Theodoridis, Phaedra R.. University of Miami; Estados Unidos
Fil: Ho, J.J. David. University of Miami; Estados Unidos
Fil: Verdun, Ramiro E.. University of Miami; Estados Unidos
Fil: Hare, Joshua M.. University of Miami; Estados Unidos
Fil: Cesarman, Ethel. Weill Cornell Medicine; Estados Unidos
Fil: Lee, Stephen. University of Miami; Estados Unidos
Fil: Mesri, Enrique Alfredo. University of Miami; Estados Unidos
description Kaposi's sarcoma herpesvirus (KSHV) is an angiogenesis-inducing oncovirus whose ability to usurp the oxygen-sensing machinery is central to its oncogenicity. By upregulating the hypoxia-inducible factors (HIFs), KSHV reprograms infected cells to a hypoxia-like state, triggering angiogenesis. Here we identify a link between KSHV replicative biology and oncogenicity by showing that KSHV's ability to regulate HIF2α levels and localization to the endoplasmic reticulum (ER) in normoxia enables translation of viral lytic mRNAs through the HIF2α-regulated eIF4E2 translation-initiation complex. This mechanism of translation in infected cells is critical for lytic protein synthesis and contributes to KSHV-induced PDGFRA activation and VEGF secretion. Thus, KSHV regulation of the oxygen-sensing machinery allows virally infected cells to initiate translation via the mTOR-dependent eIF4E1 or the HIF2α-dependent, mTOR-independent, eIF4E2. This “translation initiation plasticity” (TRIP) is an oncoviral strategy used to optimize viral protein expression that links molecular strategies of viral replication to angiogenicity and oncogenesis.
publishDate 2021
dc.date.none.fl_str_mv 2021-12
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/11336/181803
Méndez Solís, Omayra; Bendjennat, Mourad; Naipauer, Julian; Theodoridis, Phaedra R.; Ho, J.J. David; et al.; Kaposi's sarcoma herpesvirus activates the hypoxia response to usurp HIF2α-dependent translation initiation for replication and oncogenesis; Elsevier Science; Cell Reports; 37; 13; 12-2021; 1-30
2211-1247
CONICET Digital
CONICET
url http://hdl.handle.net/11336/181803
identifier_str_mv Méndez Solís, Omayra; Bendjennat, Mourad; Naipauer, Julian; Theodoridis, Phaedra R.; Ho, J.J. David; et al.; Kaposi's sarcoma herpesvirus activates the hypoxia response to usurp HIF2α-dependent translation initiation for replication and oncogenesis; Elsevier Science; Cell Reports; 37; 13; 12-2021; 1-30
2211-1247
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/S2211124721016405
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.celrep.2021.110144
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Science
publisher.none.fl_str_mv 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
_version_ 1842269352870543360
score 13.13397

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