NPF motifs in the vaccinia virus protein A36 recruit intersectin-1 to promote Cdc42:N-WASP-mediated viral release from infected cells.

Snetkov, Xenia; Weisswange, Ina; Pfanzelter, Julia; Humphries, Ashley C; Way, Michael

Snetkov, Xenia; Weisswange, Ina; Pfanzelter, Julia; Humphries, Ashley C; Way, Michael.

Afiliación

Snetkov X; Cellular Signalling and Cytoskeletal Function Laboratory, The Francis Crick Institute, Lincoln's Inn Fields Laboratory, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
Weisswange I; Cellular Signalling and Cytoskeletal Function Laboratory, The Francis Crick Institute, Lincoln's Inn Fields Laboratory, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
Pfanzelter J; Cellular Signalling and Cytoskeletal Function Laboratory, The Francis Crick Institute, Lincoln's Inn Fields Laboratory, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
Humphries AC; Cellular Signalling and Cytoskeletal Function Laboratory, The Francis Crick Institute, Lincoln's Inn Fields Laboratory, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
Way M; Cellular Signalling and Cytoskeletal Function Laboratory, The Francis Crick Institute, Lincoln's Inn Fields Laboratory, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.

Nat Microbiol ; 1(10): 16141, 2016 08 15.

Article en En | MEDLINE | ID: mdl-27670116

RESUMEN

During its egress, vaccinia virus transiently recruits AP-2 and clathrin after fusion with the plasma membrane. This recruitment polarizes the viral protein A36 beneath the virus, enhancing actin polymerization and the spread of infection. We now demonstrate that three NPF motifs in the C-terminus of A36 recruit AP-2 and clathrin by interacting directly with the Epsin15 homology domains of Eps15 and intersectin-1. A36 is the first identified viral NPF motif containing protein shown to interact with endocytic machinery. Vaccinia still induces actin tails in the absence of the A36 NPF motifs. Their loss, however, reduces the cell-to-cell spread of vaccinia. This is due to a significant reduction in virus release from infected cells, as the lack of intersectin-1 recruitment leads to a loss of Cdc42 activation, impairing N-WASP-driven Arp2/3-mediated actin polymerization. Our results suggest that initial A36-mediated virus release plays a more important role than A36-driven super-repulsion in promoting the cell-to-cell spread of vaccinia.

Asunto(s)

Proteínas Adaptadoras del Transporte Vesicular/metabolismo; Secuencias de Aminoácidos; Virus Vaccinia/fisiología; Proteínas Estructurales Virales/metabolismo; Liberación del Virus; Actinas/metabolismo; Proteínas Adaptadoras Transductoras de Señales/metabolismo; Clatrina/metabolismo; Células HeLa; Interacciones Huésped-Patógeno; Humanos; Unión Proteica; Virus Vaccinia/química; Virus Vaccinia/genética; Proteínas Estructurales Virales/química; Proteínas Estructurales Virales/genética; Proteína del Síndrome de Wiskott-Aldrich/metabolismo; Proteína de Unión al GTP cdc42/metabolismo

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Virus Vaccinia / Proteínas Estructurales Virales / Secuencias de Aminoácidos / Proteínas Adaptadoras del Transporte Vesicular / Liberación del Virus Límite: Humans Idioma: En Revista: Nat Microbiol Año: 2016 Tipo del documento: Article Pais de publicación: Reino Unido

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