Clathrin mediates infectious hepatitis C virus particle egress
Entity
UAM. Departamento de Medicina; Instituto de Investigación del Hospital de La Princesa (IP); Centro de Biología Molecular Severo Ochoa (CBM)Publisher
American Society for MicrobiologyDate
2015-01-01Citation
10.1128/JVI.03620-14
Journal of Virology 89.8 (2015): 4180-4190
ISSN
0022-538X; 1098-5514 (on line)DOI
10.1128/JVI.03620-14Funded by
This work was supported in part by the following grants: (i) grant SAF2010-21249 from the Ministerio de Ciencia e Investigación (MCI) to M.L.-C.; (ii) grant SAF2010-19270 from the MCI to P.G.; (iii) Marie Curie Career Integration grant PCIG-9-GA-2011-293664 from the European Union 7th Framework Programme for Research to P.G.; and (iv) FEDER funds via the Spanish Government to projects PI10/00101 and PI13/ 00159, from the Instituto de Salud Carlos III (ISCIII) Fondo de Investigaciónes Sanitarias (FIS) and the Fundación Mutua Madrileña, to P.L.M. I.B. was financially supported by Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas (CIBERehd), V.G. by FIS (PI10/00101), and F.M.-J. by ISCIII and Fundación para la Investigación Biomédica (FIB) del Hospital Universitario de la PrincesaProject
Gobierno de España. SAF2010-21249; Gobierno de España. SAF2010-19270; info:eu-repo/grantAgreement/EC/FP7/293664; Gobierno de España. PI10/0010Editor's Version
http://dx.doi.org/10.1128/JVI.03620-14.Subjects
Hepatitis C; Clathrin; ApoE; MedicinaRights
© 2015, American Society for Microbiology.Abstract
Although it is well established that hepatitis C virus (HCV) entry into hepatocytes depends on clathrin-mediated endocytosis,
the possible roles of clathrin in other steps of the viral cycle remain unexplored. Thus, we studied whether cell culture-derived
HCV (HCVcc) exocytosis was altered after clathrin interference. Knockdown of clathrin or the clathrin adaptor AP-1 in HCVccinfected
human hepatoma cell cultures impaired viral secretion without altering intracellular HCVcc levels or apolipoprotein B
(apoB) and apoE exocytosis. Similar reductions in HCVcc secretion were observed after treatment with specific clathrin and dynamin
inhibitors. Furthermore, detergent-free immunoprecipitation assays, neutralization experiments, and immunofluorescence
analyses suggested that whereas apoE associated with infectious intracellular HCV precursors in endoplasmic reticulum
(ER)-related structures, AP-1 participated in HCVcc egress in a post-ER compartment. Finally, we observed that clathrin and
AP-1 knockdown altered the endosomal distribution of HCV core, reducing and increasing its colocalization with early endosome
and lysosome markers, respectively. Our data support a model in which nascent HCV particles associate with apoE in the
ER and exit cells following a clathrin-dependent transendosomal secretory route
Files in this item
Google Scholar:Benedicto, Ignacio
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Gondar, Virgínia
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Molina-Jiménez, Francisca
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García-Buey, Luisa
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López-Cabrera, Manuel
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Gastaminza, Pablo
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Majano, Pedro L.
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