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dc.contributor.author
Méndez Solís, Omayra  
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Bendjennat, Mourad  
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Naipauer, Julian  
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Theodoridis, Phaedra R.  
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Ho, J.J. David  
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Verdun, Ramiro E.  
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Hare, Joshua M.  
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Cesarman, Ethel  
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Lee, Stephen  
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Mesri, Enrique Alfredo  
dc.date.available
2022-12-19T17:40:18Z  
dc.date.issued
2021-12  
dc.identifier.citation
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  
dc.identifier.issn
2211-1247  
dc.identifier.uri
http://hdl.handle.net/11336/181803  
dc.description.abstract
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.  
dc.format
application/pdf  
dc.language.iso
eng  
dc.publisher
Elsevier Science  
dc.rights
info:eu-repo/semantics/openAccess  
dc.rights.uri
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/  
dc.subject
EIF4E2 CAP BINDING  
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EPAS1  
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HHV-8  
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HYPOXIA-INDUCIBLE FACTORS  
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KAPOSI'S SARCOMA HERPESVIRUS  
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KSHV  
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OXYGEN-REGULATED TRANSLATION INITIATION  
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PDGFRA  
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VIRAL ONCOGENESIS  
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VIRAL REPLICATION  
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Virología  
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Ciencias Biológicas  
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CIENCIAS NATURALES Y EXACTAS  
dc.title
Kaposi's sarcoma herpesvirus activates the hypoxia response to usurp HIF2α-dependent translation initiation for replication and oncogenesis  
dc.type
info:eu-repo/semantics/article  
dc.type
info:ar-repo/semantics/artículo  
dc.type
info:eu-repo/semantics/publishedVersion  
dc.date.updated
2022-09-23T14:24:43Z  
dc.journal.volume
37  
dc.journal.number
13  
dc.journal.pagination
1-30  
dc.journal.pais
Países Bajos  
dc.journal.ciudad
Ámsterdam  
dc.description.fil
Fil: Méndez Solís, Omayra. University of Miami; Estados Unidos  
dc.description.fil
Fil: Bendjennat, Mourad. University of Miami; Estados Unidos  
dc.description.fil
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  
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Fil: Theodoridis, Phaedra R.. University of Miami; Estados Unidos  
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Fil: Ho, J.J. David. University of Miami; Estados Unidos  
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Fil: Verdun, Ramiro E.. University of Miami; Estados Unidos  
dc.description.fil
Fil: Hare, Joshua M.. University of Miami; Estados Unidos  
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Fil: Cesarman, Ethel. Weill Cornell Medicine; Estados Unidos  
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Fil: Lee, Stephen. University of Miami; Estados Unidos  
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Fil: Mesri, Enrique Alfredo. University of Miami; Estados Unidos  
dc.journal.title
Cell Reports  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S2211124721016405  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.celrep.2021.110144