RT info:eu-repo/semantics/article
T1 The HDAC6/APOBEC3G complex regulates HIV-1 infectiveness by inducing Vif autophagic degradation.
A1 Valenzuela Fernández, Agustín
A1 Valera, María‑Soledad
A1 Armas Rillo, Laura de
A1 Barroso González, Jonathan
A1 Ziglio, Serena
A1 Batisse, Julien
A1 Dubois, Noé
A1 Marrero Hernández, Sara
A1 Borel, Sophie
A1 García Expósito, Laura
A1 Biard‑Piechaczyk, Martine
A1 Paillart, Jean‑Christophe
A2 Medicina Física y Farmacología
A2 Grupo "Inmunología Celular y Viral".
K1 HIV-1
K1 HDAC6
K1 APOBEC3G
K1 Vif
K1 CBF-β
K1 Anti-HIV-1 restriction complex
K1 Autophagic clearance
AB Background: Human immunodeficiency virus type 1 (HIV-1) has evolved a complex strategy to overcome theimmune barriers it encounters throughout an organism thanks to its viral infectivity factor (Vif ), a key protein for HIV-1infectivity 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 A3Grestriction activity against HIV-1.Results: We found that cellular histone deacetylase 6 (HDAC6) directly interacts with A3G through its C-terminal BUZdomain (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 accountsfor 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 Vifwithout affecting the core binding factor β (CBF-β), a Vif-associated partner reported to be key for Vif- mediated A3Gdegradation. Thus HDAC6 antagonizes the proviral activity of Vif/CBF-β-associated complex by targeting Vif andstabilizing A3G. Finally, in cells producing virions, we observed a clear-cut correlation between the ability of HDAC6to degrade Vif and to restore A3G expression, suggesting that HDAC6 controls the amount of Vif incorporated intonascent virions and the ability of HIV-1 particles of being infectious. This effect seems independent on the presence ofA3G inside virions and on viral tropism.Conclusions: Our study identifies for the first time a new cellular complex, HDAC6/A3G, involved in the autophagicdegradation of Vif, and suggests that HDAC6 represents a new antiviral factor capable of controlling HIV-1 infective‑ness by counteracting Vif and its functions.
YR 2015
FD 2015
LK http://riull.ull.es/xmlui/handle/915/35374
UL http://riull.ull.es/xmlui/handle/915/35374
LA en
DS Repositorio institucional de la Universidad de La Laguna
RD 29-jun-2024