Galectin-1 exerts inhibitory effects during DENV-1 infection
Autor(a) principal: | |
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Data de Publicação: | 2014 |
Outros Autores: | , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0112474 http://hdl.handle.net/11449/126763 |
Resumo: | Dengue virus (DENV) is an enveloped RNA virus that is mosquito-transmitted and can infect a variety of immune and non-immune cells. Response to infection ranges from asymptomatic disease to a severe disorder known as dengue hemorrhagic fever. Despite efforts to control the disease, there are no effective treatments or vaccines. In our search for new antiviral compounds to combat infection by dengue virus type 1 (DENV-1), we investigated the role of galectin-1, a widely-expressed mammalian lectin with functions in cell-pathogen interactions and immunoregulatory properties. We found that DENV-1 infection of cells in vitro exhibited caused decreased expression of Gal-1 in several different human cell lines, suggesting that loss of Gal-1 is associated with virus production. In test of this hypothesis we found that exogenous addition of human recombinant Gal-1 (hrGal-1) inhibits the virus production in the three different cell types. This inhibitory effect was dependent on hrGal-1 dimerization and required its carbohydrate recognition domain. Importantly, the inhibition was specific for hrGal-1, since no effect was observed using recombinant human galectin-3. Interestingly, we found that hrGal-1 directly binds to dengue virus and acts, at least in part, during the early stages of DENV-1 infection, by inhibiting viral adsorption and its internalization to target cells. To test the in vivo role of Gal-1 in DENV infection, Gal-1-deficient-mice were used to demonstrate that the expression of endogenous Galectin-1 contributes to resistance of macrophages to in vitro-infection with DENV-1 and it is also important to physiological susceptibility of mice to in vivo infection with DENV-1. These results provide novel insights into the functions of Gal-1 in resistance to DENV infection and suggest that Gal-1 should be explored as a potential antiviral compound. |
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Galectin-1 exerts inhibitory effects during DENV-1 infectionDengue virus (DENV) is an enveloped RNA virus that is mosquito-transmitted and can infect a variety of immune and non-immune cells. Response to infection ranges from asymptomatic disease to a severe disorder known as dengue hemorrhagic fever. Despite efforts to control the disease, there are no effective treatments or vaccines. In our search for new antiviral compounds to combat infection by dengue virus type 1 (DENV-1), we investigated the role of galectin-1, a widely-expressed mammalian lectin with functions in cell-pathogen interactions and immunoregulatory properties. We found that DENV-1 infection of cells in vitro exhibited caused decreased expression of Gal-1 in several different human cell lines, suggesting that loss of Gal-1 is associated with virus production. In test of this hypothesis we found that exogenous addition of human recombinant Gal-1 (hrGal-1) inhibits the virus production in the three different cell types. This inhibitory effect was dependent on hrGal-1 dimerization and required its carbohydrate recognition domain. Importantly, the inhibition was specific for hrGal-1, since no effect was observed using recombinant human galectin-3. Interestingly, we found that hrGal-1 directly binds to dengue virus and acts, at least in part, during the early stages of DENV-1 infection, by inhibiting viral adsorption and its internalization to target cells. To test the in vivo role of Gal-1 in DENV infection, Gal-1-deficient-mice were used to demonstrate that the expression of endogenous Galectin-1 contributes to resistance of macrophages to in vitro-infection with DENV-1 and it is also important to physiological susceptibility of mice to in vivo infection with DENV-1. These results provide novel insights into the functions of Gal-1 in resistance to DENV infection and suggest that Gal-1 should be explored as a potential antiviral compound.Universidade Estadual Paulista Júlio de Mesquita Filho, Faculdade de Ciências e Letras de Assis, Assis, Avenida Dom Antonio, 2100, Parque Universitário, CEP 19806900, SP, BrasilUniversidade Estadual Paulista Júlio de Mesquita Filho, Faculdade de Ciências e Letras de Assis, Assis, Avenida Dom Antonio, 2100, Parque Universitário, CEP 19806900, SP, BrasilUniversidade Estadual Paulista (Unesp)Toledo, Karina Alves de [UNESP]Fermino, Marise LopesAndrade, Camillo Del CistiaRiul, Thalita BachelliAlves, Renata ToméMuller, Vanessa Danielle MenjonRusso, Raquel RinaldiStowell, Sean R.Cummings, Richard D.Aquino, Victor HugoDias-baruffi, Marcelo2015-08-21T17:53:06Z2015-08-21T17:53:06Z2014info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlee112474http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0112474Plos One, v. 9, n. 11, p. e112474, 2014.1932-6203http://hdl.handle.net/11449/12676310.1371/journal.pone.011247457725657743040200000-0001-7212-6794Currículo Lattesreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengPlos One2.7661,164info:eu-repo/semantics/openAccess2024-06-13T17:38:54Zoai:repositorio.unesp.br:11449/126763Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T22:52:25.099297Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Galectin-1 exerts inhibitory effects during DENV-1 infection |
title |
Galectin-1 exerts inhibitory effects during DENV-1 infection |
spellingShingle |
Galectin-1 exerts inhibitory effects during DENV-1 infection Toledo, Karina Alves de [UNESP] |
title_short |
Galectin-1 exerts inhibitory effects during DENV-1 infection |
title_full |
Galectin-1 exerts inhibitory effects during DENV-1 infection |
title_fullStr |
Galectin-1 exerts inhibitory effects during DENV-1 infection |
title_full_unstemmed |
Galectin-1 exerts inhibitory effects during DENV-1 infection |
title_sort |
Galectin-1 exerts inhibitory effects during DENV-1 infection |
author |
Toledo, Karina Alves de [UNESP] |
author_facet |
Toledo, Karina Alves de [UNESP] Fermino, Marise Lopes Andrade, Camillo Del Cistia Riul, Thalita Bachelli Alves, Renata Tomé Muller, Vanessa Danielle Menjon Russo, Raquel Rinaldi Stowell, Sean R. Cummings, Richard D. Aquino, Victor Hugo Dias-baruffi, Marcelo |
author_role |
author |
author2 |
Fermino, Marise Lopes Andrade, Camillo Del Cistia Riul, Thalita Bachelli Alves, Renata Tomé Muller, Vanessa Danielle Menjon Russo, Raquel Rinaldi Stowell, Sean R. Cummings, Richard D. Aquino, Victor Hugo Dias-baruffi, Marcelo |
author2_role |
author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) |
dc.contributor.author.fl_str_mv |
Toledo, Karina Alves de [UNESP] Fermino, Marise Lopes Andrade, Camillo Del Cistia Riul, Thalita Bachelli Alves, Renata Tomé Muller, Vanessa Danielle Menjon Russo, Raquel Rinaldi Stowell, Sean R. Cummings, Richard D. Aquino, Victor Hugo Dias-baruffi, Marcelo |
description |
Dengue virus (DENV) is an enveloped RNA virus that is mosquito-transmitted and can infect a variety of immune and non-immune cells. Response to infection ranges from asymptomatic disease to a severe disorder known as dengue hemorrhagic fever. Despite efforts to control the disease, there are no effective treatments or vaccines. In our search for new antiviral compounds to combat infection by dengue virus type 1 (DENV-1), we investigated the role of galectin-1, a widely-expressed mammalian lectin with functions in cell-pathogen interactions and immunoregulatory properties. We found that DENV-1 infection of cells in vitro exhibited caused decreased expression of Gal-1 in several different human cell lines, suggesting that loss of Gal-1 is associated with virus production. In test of this hypothesis we found that exogenous addition of human recombinant Gal-1 (hrGal-1) inhibits the virus production in the three different cell types. This inhibitory effect was dependent on hrGal-1 dimerization and required its carbohydrate recognition domain. Importantly, the inhibition was specific for hrGal-1, since no effect was observed using recombinant human galectin-3. Interestingly, we found that hrGal-1 directly binds to dengue virus and acts, at least in part, during the early stages of DENV-1 infection, by inhibiting viral adsorption and its internalization to target cells. To test the in vivo role of Gal-1 in DENV infection, Gal-1-deficient-mice were used to demonstrate that the expression of endogenous Galectin-1 contributes to resistance of macrophages to in vitro-infection with DENV-1 and it is also important to physiological susceptibility of mice to in vivo infection with DENV-1. These results provide novel insights into the functions of Gal-1 in resistance to DENV infection and suggest that Gal-1 should be explored as a potential antiviral compound. |
publishDate |
2014 |
dc.date.none.fl_str_mv |
2014 2015-08-21T17:53:06Z 2015-08-21T17:53:06Z |
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://journals.plos.org/plosone/article?id=10.1371/journal.pone.0112474 Plos One, v. 9, n. 11, p. e112474, 2014. 1932-6203 http://hdl.handle.net/11449/126763 10.1371/journal.pone.0112474 5772565774304020 0000-0001-7212-6794 |
url |
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0112474 http://hdl.handle.net/11449/126763 |
identifier_str_mv |
Plos One, v. 9, n. 11, p. e112474, 2014. 1932-6203 10.1371/journal.pone.0112474 5772565774304020 0000-0001-7212-6794 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Plos One 2.766 1,164 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
e112474 |
dc.source.none.fl_str_mv |
Currículo Lattes reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
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1808129468765569024 |