The CD63-Syntenin-1 Complex Controls Post-Endocytic Trafficking of Oncogenic Human Papillomaviruses.

Gräßel, Linda; Fast, Laura Aline; Scheffer, Konstanze D; Boukhallouk, Fatima; Spoden, Gilles A; Tenzer, Stefan; Boller, Klaus; Bago, Ruzica; Rajesh, Sundaresan; Overduin, Michael; Berditchevski, Fedor; Florin, Luise

Gräßel, Linda; Fast, Laura Aline; Scheffer, Konstanze D; Boukhallouk, Fatima; Spoden, Gilles A; Tenzer, Stefan; Boller, Klaus; Bago, Ruzica; Rajesh, Sundaresan; Overduin, Michael; Berditchevski, Fedor; Florin, Luise.

Afiliación

Gräßel L; Department of Medical Microbiology and Hygiene, University Medical Centre of the Johannes Gutenberg University, Mainz, Germany.
Fast LA; Department of Medical Microbiology and Hygiene, University Medical Centre of the Johannes Gutenberg University, Mainz, Germany.
Scheffer KD; Department of Medical Microbiology and Hygiene, University Medical Centre of the Johannes Gutenberg University, Mainz, Germany.
Boukhallouk F; Department of Medical Microbiology and Hygiene, University Medical Centre of the Johannes Gutenberg University, Mainz, Germany.
Spoden GA; Department of Medical Microbiology and Hygiene, University Medical Centre of the Johannes Gutenberg University, Mainz, Germany.
Tenzer S; Department of Immunology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
Boller K; Paul Ehrlich Institute, Langen, Germany.
Bago R; School of Cancer Sciences and Department of Pathology, The University of Birmingham, Birmingham, United Kingdom.
Rajesh S; School of Cancer Sciences and Department of Pathology, The University of Birmingham, Birmingham, United Kingdom.
Overduin M; Department of Biochemistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada.
Berditchevski F; School of Cancer Sciences and Department of Pathology, The University of Birmingham, Birmingham, United Kingdom.
Florin L; Department of Medical Microbiology and Hygiene, University Medical Centre of the Johannes Gutenberg University, Mainz, Germany.

Sci Rep ; 6: 32337, 2016 08 31.

Article en En | MEDLINE | ID: mdl-27578500

RESUMEN

Human papillomaviruses enter host cells via a clathrin-independent endocytic pathway involving tetraspanin proteins. However, post-endocytic trafficking required for virus capsid disassembly remains unclear. Here we demonstrate that the early trafficking pathway of internalised HPV particles involves tetraspanin CD63, syntenin-1 and ESCRT-associated adaptor protein ALIX. Following internalisation, viral particles are found in CD63-positive endosomes recruiting syntenin-1, a CD63-interacting adaptor protein. Electron microscopy and immunofluorescence experiments indicate that the CD63-syntenin-1 complex controls delivery of internalised viral particles to multivesicular endosomes. Accordingly, infectivity of high-risk HPV types 16, 18 and 31 as well as disassembly and post-uncoating processing of viral particles was markedly suppressed in CD63 or syntenin-1 depleted cells. Our analyses also present the syntenin-1 interacting protein ALIX as critical for HPV infection and CD63-syntenin-1-ALIX complex formation as a prerequisite for intracellular transport enabling viral capsid disassembly. Thus, our results identify the CD63-syntenin-1-ALIX complex as a key regulatory component in post-endocytic HPV trafficking.

Asunto(s)

Proteínas de Unión al Calcio/genética; Proteínas de Ciclo Celular/genética; Complejos de Clasificación Endosomal Requeridos para el Transporte/genética; Infecciones por Papillomavirus/genética; Sinteninas/genética; Tetraspanina 30/genética; Neoplasias del Cuello Uterino/genética; Proteínas de Unión al Calcio/química; Carcinogénesis/genética; Proteínas de Ciclo Celular/química; Endocitosis/genética; Complejos de Clasificación Endosomal Requeridos para el Transporte/química; Femenino; Células HeLa; Papillomavirus Humano 16/genética; Papillomavirus Humano 16/patogenicidad; Papillomavirus Humano 18/genética; Papillomavirus Humano 18/patogenicidad; Papillomavirus Humano 31/genética; Papillomavirus Humano 31/patogenicidad; Humanos; Complejos Multiproteicos/química; Complejos Multiproteicos/genética; Infecciones por Papillomavirus/patología; Infecciones por Papillomavirus/virología; Unión Proteica; Transporte de Proteínas/genética; Tetraspanina 30/química; Neoplasias del Cuello Uterino/patología; Neoplasias del Cuello Uterino/virología

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas de Unión al Calcio / Neoplasias del Cuello Uterino / Proteínas de Ciclo Celular / Infecciones por Papillomavirus / Sinteninas / Complejos de Clasificación Endosomal Requeridos para el Transporte / Tetraspanina 30 Límite: Female / Humans Idioma: En Revista: Sci Rep Año: 2016 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido

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