Galectin-1 exerts inhibitory effects during DENV-1 infection

Detalhes bibliográficos
Autor(a) principal: Toledo, Karina Alves de [UNESP]
Data de Publicação: 2014
Outros Autores: 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
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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spelling 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
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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
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dc.source.none.fl_str_mv Currículo Lattes
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