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dc.contributor.authorValenzuela Fernández, Agustín 
dc.contributor.authorValera, María‑Soledad
dc.contributor.authorArmas Rillo, Laura de
dc.contributor.authorBarroso González, Jonathan
dc.contributor.authorZiglio, Serena
dc.contributor.authorBatisse, Julien
dc.contributor.authorDubois, Noé
dc.contributor.authorMarrero Hernández, Sara 
dc.contributor.authorBorel, Sophie
dc.contributor.authorGarcía Expósito, Laura
dc.contributor.authorBiard‑Piechaczyk, Martine
dc.contributor.authorPaillart, Jean‑Christophe
dc.contributor.otherMedicina Física y Farmacología
dc.contributor.otherGrupo "Inmunología Celular y Viral".
dc.date.accessioned2024-01-15T21:10:35Z
dc.date.available2024-01-15T21:10:35Z
dc.date.issued2015
dc.identifier.urihttp://riull.ull.es/xmlui/handle/915/35374
dc.description.abstractBackground: Human immunodeficiency virus type 1 (HIV-1) has evolved a complex strategy to overcome the immune barriers it encounters throughout an organism thanks to its viral infectivity factor (Vif ), a key protein for HIV-1 infectivity and in vivo pathogenesis. Vif interacts with and promotes “apolipoprotein B mRNA-editing enzyme-cata‑ lytic, polypeptide-like 3G” (A3G) ubiquitination and subsequent degradation by the proteasome, thus eluding A3G restriction activity against HIV-1. Results: We found that cellular histone deacetylase 6 (HDAC6) directly interacts with A3G through its C-terminal BUZ domain (residues 841–1,215) to undergo a cellular co-distribution along microtubules and cytoplasm. The HDAC6/ A3G complex occurs in the absence or presence of Vif, competes for Vif-mediated A3G degradation, and accounts for A3G steady-state expression level. In fact, HDAC6 directly interacts with and promotes Vif autophagic clearance, thanks to its C-terminal BUZ domain, a process requiring the deacetylase activity of HDAC6. HDAC6 degrades Vif without affecting the core binding factor β (CBF-β), a Vif-associated partner reported to be key for Vif- mediated A3G degradation. Thus HDAC6 antagonizes the proviral activity of Vif/CBF-β-associated complex by targeting Vif and stabilizing A3G. Finally, in cells producing virions, we observed a clear-cut correlation between the ability of HDAC6 to degrade Vif and to restore A3G expression, suggesting that HDAC6 controls the amount of Vif incorporated into nascent virions and the ability of HIV-1 particles of being infectious. This effect seems independent on the presence of A3G inside virions and on viral tropism. Conclusions: Our study identifies for the first time a new cellular complex, HDAC6/A3G, involved in the autophagic degradation of Vif, and suggests that HDAC6 represents a new antiviral factor capable of controlling HIV-1 infective‑ ness by counteracting Vif and its functions.en
dc.format.mimetypeapplication/pdf
dc.language.isoen
dc.relation.ispartofseriesValera et al. Retrovirology (2015) 12:53
dc.rightsLicencia Creative Commons (Reconocimiento-No comercial-Sin obras derivadas 4.0 Internacional)
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/deed.es_ES
dc.titleThe HDAC6/APOBEC3G complex regulates HIV-1 infectiveness by inducing Vif autophagic degradation.en
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.1186/s12977-015-0181-5
dc.subject.keywordHIV-1en
dc.subject.keywordHDAC6en
dc.subject.keywordAPOBEC3Gen
dc.subject.keywordVifen
dc.subject.keywordCBF-βen
dc.subject.keywordAnti-HIV-1 restriction complexen
dc.subject.keywordAutophagic clearanceen


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