Molecular level evaluation of the dengue virus capsid protein role(s) on the virus life cycle

Detalhes bibliográficos
Autor(a) principal: Faustino, André Filipe da Costa
Data de Publicação: 2011
Tipo de documento: Dissertação
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/8945
Resumo: Tese de mestrado em Bioquímica, apresentada à Universidade de Lisboa, através da Faculdade de Ciências, 2011
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spelling Molecular level evaluation of the dengue virus capsid protein role(s) on the virus life cycleDengue virusCapsid proteinLipid dropletsLipoproteinsInhibitor peptideTeses de mestrado - 2011Tese de mestrado em Bioquímica, apresentada à Universidade de Lisboa, através da Faculdade de Ciências, 2011Viral hemorrhagic fever is mostly caused by dengue virus (DENV), which originates 100 million infections annually. DENV is a Flavivirus, member of the Flaviviridae family that also comprises other important human pathogens. This virus affects the host lipid metabolism, increasing intracellular lipid droplets (LDs) and imbalancing plasma lipoproteins levels and composition. Effective dengue treatments are not available yet, in part due to the poor understanding of some viral life cycle steps. The DENV capsid protein (DENV C) was recently found to interact with LDs, in a process that influences viral replication. However, the underlying molecular mechanisms of such interaction were not clear and also no function had already been attributed to its N-terminal disordered region. Moreover, human lipoproteins, similar to LDs in structure and composition, could play an important role in the dengue virus infectivity process. This study aimed at unraveling the molecular mechanism behind the DENV C protein interaction with host LDs and lipoproteins, which may explain key processes occurring in vivo. The understanding of the molecular nature and biological relevance of these interactions may also provide clues on how to inhibit them. In the present study, it was found that DENV C N-terminal region is crucial for the interaction with LDs and VLDL, requiring the presence of potassium. These interactions seem to occur mainly with LDs and VLDL intrinsic protein(s), rather than lipids. Importantly, pep14-23, a peptide based on the DENV C N-terminal conserved region, inhibits the C-LDs interaction. In contact with negative phospholipids, this peptide undergoes a structural conversion to α-helix. This lipid-driven structural conversion may thus help pep14-23 interaction with its target. These are clear breakthroughs in the understanding of DENV C-LDs interaction (and inhibition), providing a ground for the development of C protein targeted treatments for the infections by DENV and other Flavivirus.Santos, Nuno C., 1972-Almeida, Rodrigo Freire Martins deRepositório da Universidade de LisboaFaustino, André Filipe da Costa2013-08-02T10:23:17Z20112011-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10451/8945engmetadata only accessinfo: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:RCAAP2023-11-08T15:53:02Zoai:repositorio.ul.pt:10451/8945Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:33:17.924262Repositório 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 Molecular level evaluation of the dengue virus capsid protein role(s) on the virus life cycle
title Molecular level evaluation of the dengue virus capsid protein role(s) on the virus life cycle
spellingShingle Molecular level evaluation of the dengue virus capsid protein role(s) on the virus life cycle
Faustino, André Filipe da Costa
Dengue virus
Capsid protein
Lipid droplets
Lipoproteins
Inhibitor peptide
Teses de mestrado - 2011
title_short Molecular level evaluation of the dengue virus capsid protein role(s) on the virus life cycle
title_full Molecular level evaluation of the dengue virus capsid protein role(s) on the virus life cycle
title_fullStr Molecular level evaluation of the dengue virus capsid protein role(s) on the virus life cycle
title_full_unstemmed Molecular level evaluation of the dengue virus capsid protein role(s) on the virus life cycle
title_sort Molecular level evaluation of the dengue virus capsid protein role(s) on the virus life cycle
author Faustino, André Filipe da Costa
author_facet Faustino, André Filipe da Costa
author_role author
dc.contributor.none.fl_str_mv Santos, Nuno C., 1972-
Almeida, Rodrigo Freire Martins de
Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Faustino, André Filipe da Costa
dc.subject.por.fl_str_mv Dengue virus
Capsid protein
Lipid droplets
Lipoproteins
Inhibitor peptide
Teses de mestrado - 2011
topic Dengue virus
Capsid protein
Lipid droplets
Lipoproteins
Inhibitor peptide
Teses de mestrado - 2011
description Tese de mestrado em Bioquímica, apresentada à Universidade de Lisboa, através da Faculdade de Ciências, 2011
publishDate 2011
dc.date.none.fl_str_mv 2011
2011-01-01T00:00:00Z
2013-08-02T10:23:17Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/8945
url http://hdl.handle.net/10451/8945
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv metadata only access
info:eu-repo/semantics/openAccess
rights_invalid_str_mv metadata only access
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
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