Galectin-1 exerts inhibitory effects during DENV-1 infection
| Autor: | Camillo Del Cistia Andrade, Marcelo Dias-Baruffi, Thalita B. Riul, Karina Alves Toledo, Sean R. Stowell, Raquel Rinaldi Russo, Richard D. Cummings, Renata Tomé Alves, Victor Hugo Aquino, Marise Lopes Fermino, Vanessa Danielle Menjon Muller |
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| Přispěvatelé: | Universidade Estadual Paulista (Unesp) |
| Rok vydání: | 2014 |
| Předmět: |
Viral Diseases
Galectin 1 Galectin 3 viruses Glycobiology lcsh:Medicine Pathogenesis Dengue virus Pathology and Laboratory Medicine medicine.disease_cause Biochemistry Dengue Fever Dengue fever Dengue Mice Medicine and Health Sciences lcsh:Science Multidisciplinary Cell Death biology Flow Cytometry Recombinant Proteins Infectious Diseases Host-Pathogen Interactions Viral load Research Article Neglected Tropical Diseases Cell Survival Carbohydrates Enzyme-Linked Immunosorbent Assay Mice Transgenic CARBOIDRATOS Microbiology Antiviral Agents Virus Cell Line Immune system In vivo Virology medicine Animals Humans Cell Lineage Antibody-dependent enhancement Macrophages Host Cells lcsh:R Biology and Life Sciences RNA virus Dengue Virus Tropical Diseases biology.organism_classification medicine.disease Viral Replication Mice Inbred C57BL Animal Models of Infection lcsh:Q Adsorption Viral Transmission and Infection |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP Currículo Lattes Repositório Institucional da UNESP Universidade Estadual Paulista (UNESP) instacron:UNESP PLoS ONE, Vol 9, Iss 11, p e112474 (2014) PLoS ONE |
| Popis: | Made available in DSpace on 2015-08-21T17:53:06Z (GMT). No. of bitstreams: 0 Previous issue date: 2014 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. Universidade Estadual Paulista Júlio de Mesquita Filho, Faculdade de Ciências e Letras de Assis, Assis, Avenida Dom Antonio, 2100, Parque Universitário, CEP 19806900, SP, Brasil Universidade Estadual Paulista Júlio de Mesquita Filho, Faculdade de Ciências e Letras de Assis, Assis, Avenida Dom Antonio, 2100, Parque Universitário, CEP 19806900, SP, Brasil |
| Databáze: | OpenAIRE |
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