RT info:eu-repo/semantics/article
T1 HIV-1 requires Arf6-mediated membrane dynamics to efficiently enter and infect T lymphocytes.
A1 Valenzuela Fernández, Agustín
A1 García Expósito, Laura
A1 Barroso González, Jonathan
A1 Puigdomènech, Isabel
A1 Machado, José David
A1 Blanco, Julià
A2 Medicina Física y Farmacología
A2 Grupo "Inmunología Celular y Viral".
AB As the initial barrier to viral entry, the plasma membrane along with the membrane trafficking machinery and cytoskeleton are of fundamental importance in the viral cycle.However, little is known about the contribution of plasma membrane dynamics during earlyhuman immunodeficiency virus type 1 (HIV-1) infection. Considering that ADP ribosylationfactor 6 (Arf6) regulates cellular invasion via several microorganisms by coordinating membrane trafficking, our aim was to study the function of Arf6-mediated membrane dynamics onHIV-1 entry and infection of T lymphocytes. We observed that an alteration of the Arf6–guanosine 5′-diphosphate/guanosine 5′-triphosphate (GTP/GDP) cycle, by GDP-bound orGTP-bound inactive mutants or by specific Arf6 silencing, inhibited HIV-1 envelope–inducedmembrane fusion, entry, and infection of T lymphocytes and permissive cells, regardless ofviral tropism. Furthermore, cell-to-cell HIV-1 transmission of primary human CD4+ T lymphocytes was inhibited by Arf6 knockdown. Total internal reflection fluorescence microscopyshowed that Arf6 mutants provoked the accumulation of phosphatidylinositol-(4,5)-biphosphate–associated structures on the plasma membrane of permissive cells, without affectingCD4-viral attachment but impeding CD4-dependent HIV-1 entry. Arf6 silencing or its mutantsdid not affect fusion, entry, and infection of vesicular stomatitis virus G–pseudotyped virusesor ligand-induced CXCR4 or CCR5 endocytosis, both clathrin-dependent processes. Thereforewe propose that efficient early HIV-1 infection of CD4+ T lymphocytes requires Arf6-coordinated plasma membrane dynamics that promote viral fusion and entry.
YR 2011
FD 2011
LK http://riull.ull.es/xmlui/handle/915/35360
UL http://riull.ull.es/xmlui/handle/915/35360
LA en
DS Repositorio institucional de la Universidad de La Laguna
RD 27-jun-2024