Dengue virus capsid protein binding to hepatic lipid droplets (LD) is potassium ion dependent and is mediated by LD surface proteins
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2012 |
| Outros Autores: | , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/10451/10765 |
Resumo: | Copyright © 2012, American Society for Microbiology. All Rights Reserved. |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Dengue virus capsid protein binding to hepatic lipid droplets (LD) is potassium ion dependent and is mediated by LD surface proteinsCopyright © 2012, American Society for Microbiology. All Rights Reserved.Dengue virus (DENV) affects millions of people, causing more than 20,000 deaths annually. No effective treatment for the disease caused by DENV infection is currently available, partially due to the lack of knowledge on the basic aspects of the viral life cycle, including the molecular basis of the interaction between viral components and cellular compartments. Here, we characterized the properties of the interaction between the DENV capsid (C) protein and hepatic lipid droplets (LDs), which was recently shown to be essential for the virus replication cycle. Zeta potential analysis revealed a negative surface charge of LDs, with an average surface charge of -19 mV. The titration of LDs with C protein led to an increase of the surface charge, which reached a plateau at +13.7 mV, suggesting that the viral protein-LD interaction exposes the protein cationic surface to the aqueous environment. Atomic force microscopy (AFM)-based force spectroscopy measurements were performed by using C protein-functionalized AFM tips. The C protein-LD interaction was found to be strong, with a single (un)binding force of 33.6 pN. This binding was dependent on high intracellular concentrations of potassium ions but not sodium. The inhibition of Na+/K+-ATPase in DENV-infected cells resulted in the dissociation of C protein from LDs and a 50-fold inhibition of infectious virus production but not of RNA replication, indicating a biological relevance for the potassium-dependent interaction. Limited proteolysis of the LD surface impaired the C protein-LD interaction, and force measurements in the presence of specific antibodies indicated that perilipin 3 (TIP47) is the major DENV C protein ligand on the surface of LDs.This work was supported by FP7-PEOPLE IRSES (International Research Staff Exchange Scheme) project MEMPEPACROSS (European Union), by the Fundação para a Ciência e a Tecnologia—Ministério da Educação e Ciência (FCT-MEC, Portugal) (projects PTDC/QUI-BIQ/112929/2009 and PTDC/QUI/69937/2006), by Fundação Calouste Gulbenkian (Portugal), by the FCT-CAPES Portugal-Brazil joint cooperation projects, and by the Brazilian funding agencies Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação Carlos Chagas Filho de Amparo a` Pesquisa do Estado do Rio de Janeiro (FAPERJ), Financiadora de Estudos e Projetos (FINEP), and National Institute of Science and Technology in Dengue (INCT-Dengue). I. C. Martins also acknowledges consecutive postdoctoral funding from a Marie Curie International Outgoing Fellowship (MC-IOF-237373) and FCT-MEC postdoctoral fellowships (SFRH/BPD/46324/2008 and SFRH/BPD/74287/2010). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.American Society for MicrobiologyRepositório da Universidade de LisboaCarvalho, Filomena A.Carneiro, Fabiana A.Martins, Ivo C.Assunção-Miranda, IranaiaFaustino, André F.Pereira, Renata M.Bozza, Patricia T.Castanho, Miguel A. R. B.Mohana-Borges, RonaldoPoian, Andrea T. DaSantos, Nuno C.2014-03-21T11:42:07Z20122012-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/10765engJournal of Virology, 2012, p. 2096–21080022-538Xhttp://dx.doi.org/10.1128/JVI.06796-11info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T15:56:29Zoai:repositorio.ul.pt:10451/10765Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:34:41.206201Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
| dc.title.none.fl_str_mv |
Dengue virus capsid protein binding to hepatic lipid droplets (LD) is potassium ion dependent and is mediated by LD surface proteins |
| title |
Dengue virus capsid protein binding to hepatic lipid droplets (LD) is potassium ion dependent and is mediated by LD surface proteins |
| spellingShingle |
Dengue virus capsid protein binding to hepatic lipid droplets (LD) is potassium ion dependent and is mediated by LD surface proteins Carvalho, Filomena A. |
| title_short |
Dengue virus capsid protein binding to hepatic lipid droplets (LD) is potassium ion dependent and is mediated by LD surface proteins |
| title_full |
Dengue virus capsid protein binding to hepatic lipid droplets (LD) is potassium ion dependent and is mediated by LD surface proteins |
| title_fullStr |
Dengue virus capsid protein binding to hepatic lipid droplets (LD) is potassium ion dependent and is mediated by LD surface proteins |
| title_full_unstemmed |
Dengue virus capsid protein binding to hepatic lipid droplets (LD) is potassium ion dependent and is mediated by LD surface proteins |
| title_sort |
Dengue virus capsid protein binding to hepatic lipid droplets (LD) is potassium ion dependent and is mediated by LD surface proteins |
| author |
Carvalho, Filomena A. |
| author_facet |
Carvalho, Filomena A. Carneiro, Fabiana A. Martins, Ivo C. Assunção-Miranda, Iranaia Faustino, André F. Pereira, Renata M. Bozza, Patricia T. Castanho, Miguel A. R. B. Mohana-Borges, Ronaldo Poian, Andrea T. Da Santos, Nuno C. |
| author_role |
author |
| author2 |
Carneiro, Fabiana A. Martins, Ivo C. Assunção-Miranda, Iranaia Faustino, André F. Pereira, Renata M. Bozza, Patricia T. Castanho, Miguel A. R. B. Mohana-Borges, Ronaldo Poian, Andrea T. Da Santos, Nuno C. |
| author2_role |
author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
| dc.contributor.author.fl_str_mv |
Carvalho, Filomena A. Carneiro, Fabiana A. Martins, Ivo C. Assunção-Miranda, Iranaia Faustino, André F. Pereira, Renata M. Bozza, Patricia T. Castanho, Miguel A. R. B. Mohana-Borges, Ronaldo Poian, Andrea T. Da Santos, Nuno C. |
| description |
Copyright © 2012, American Society for Microbiology. All Rights Reserved. |
| publishDate |
2012 |
| dc.date.none.fl_str_mv |
2012 2012-01-01T00:00:00Z 2014-03-21T11:42:07Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
| dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10451/10765 |
| url |
http://hdl.handle.net/10451/10765 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
Journal of Virology, 2012, p. 2096–2108 0022-538X http://dx.doi.org/10.1128/JVI.06796-11 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
| dc.publisher.none.fl_str_mv |
American Society for Microbiology |
| publisher.none.fl_str_mv |
American Society for Microbiology |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799134242755575808 |