Serine proteases in neutrophil extracellular traps exhibit anti-Respiratory Syncytial Virus activity
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1016/j.intimp.2022.108573 http://hdl.handle.net/11449/223465 |
Resumo: | Human respiratory syncytial virus (hRSV) is an infectious agent in infants and young children which there are no vaccines or drugs for treatment. Neutrophils are recruited for airway, where they are stimulated by hRSV to release large amounts of neutrophil extracellular traps (NETs). NETs are compound by DNA and proteins, including microbicidal enzymes. They constitute a large part of the mucus accumulated in the lung of patients, compromising their breathing capacity. In contrast, NETs can capture/inactivate hRSV, but the molecules responsible for this effect are unknown. Objectives: We selected microbicidal NET enzymes (elastase, myeloperoxidase, cathepsin-G, and proteinase-3) to assess their anti-hRSV role. Methods and Results: Through in vitro assays using HEp-2 cells, we observed that elastase, proteinase-3, and cathepsin-G, but not myeloperoxidase, showed virucidal effects even at non-cytotoxic concentrations. Elastase and proteinase-3, but not cathepsin-G, cleaved viral F-protein, which is responsible for viral adhesion and fusion with the target cells. Molecular docking analysis indicated the interaction of these macromolecules in the antigenic regions of F-protein through the active regions of the enzymes. Conclusions: Serine proteases from NETs interact and inactive hRSV. These results contribute to the understanding the role of NETs in hRSV infection and to designing treatment strategies for the inflammatory process during respiratory infections. |
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Serine proteases in neutrophil extracellular traps exhibit anti-Respiratory Syncytial Virus activityNeutrophilsProteasesRespiratory syncytial virusVirucidalHuman respiratory syncytial virus (hRSV) is an infectious agent in infants and young children which there are no vaccines or drugs for treatment. Neutrophils are recruited for airway, where they are stimulated by hRSV to release large amounts of neutrophil extracellular traps (NETs). NETs are compound by DNA and proteins, including microbicidal enzymes. They constitute a large part of the mucus accumulated in the lung of patients, compromising their breathing capacity. In contrast, NETs can capture/inactivate hRSV, but the molecules responsible for this effect are unknown. Objectives: We selected microbicidal NET enzymes (elastase, myeloperoxidase, cathepsin-G, and proteinase-3) to assess their anti-hRSV role. Methods and Results: Through in vitro assays using HEp-2 cells, we observed that elastase, proteinase-3, and cathepsin-G, but not myeloperoxidase, showed virucidal effects even at non-cytotoxic concentrations. Elastase and proteinase-3, but not cathepsin-G, cleaved viral F-protein, which is responsible for viral adhesion and fusion with the target cells. Molecular docking analysis indicated the interaction of these macromolecules in the antigenic regions of F-protein through the active regions of the enzymes. Conclusions: Serine proteases from NETs interact and inactive hRSV. These results contribute to the understanding the role of NETs in hRSV infection and to designing treatment strategies for the inflammatory process during respiratory infections.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)São Paulo State University (UNESP) Institute of Biosciences Humanities and Exact SciencesSão Paulo State University (UNESP) School of Sciences Humanities and LanguagesGraduate Program in Applied and Computational Mathematics – PGMAC - State University of LondrinaDepartment of Medical Microbiology and Infectious Diseases University of ManitobaBiosystems Collaborative Nucleus Institute of Exact Sciences Federal University of JataiVirology Laboratory Center for Microbiology Studies Department of Parasitology Microbiology and Immunology Federal University of Juiz de Fora, Minas GeraisSão Paulo State University (UNESP) Institute of Biosciences Humanities and Exact SciencesSão Paulo State University (UNESP) School of Sciences Humanities and LanguagesFAPESP: 2018/09021-4Universidade Estadual Paulista (UNESP)Universidade Estadual de Londrina (UEL)University of ManitobaFederal University of JataiFederal University of Juiz de ForaLopes, Bruno Rafael Pereira [UNESP]da Silva, Gabriel Soares [UNESP]de Lima Menezes, Gabrielade Oliveira, Juliana [UNESP]Watanabe, Aripuanã Sakurada AranhaPorto, Bárbara Neryda Silva, Roosevelt AlvesToledo, Karina Alves [UNESP]2022-04-28T19:50:49Z2022-04-28T19:50:49Z2022-05-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.intimp.2022.108573International Immunopharmacology, v. 106.1878-17051567-5769http://hdl.handle.net/11449/22346510.1016/j.intimp.2022.1085732-s2.0-85124592170Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengInternational Immunopharmacologyinfo:eu-repo/semantics/openAccess2022-04-28T19:50:49Zoai:repositorio.unesp.br:11449/223465Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462022-04-28T19:50:49Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Serine proteases in neutrophil extracellular traps exhibit anti-Respiratory Syncytial Virus activity |
title |
Serine proteases in neutrophil extracellular traps exhibit anti-Respiratory Syncytial Virus activity |
spellingShingle |
Serine proteases in neutrophil extracellular traps exhibit anti-Respiratory Syncytial Virus activity Lopes, Bruno Rafael Pereira [UNESP] Neutrophils Proteases Respiratory syncytial virus Virucidal |
title_short |
Serine proteases in neutrophil extracellular traps exhibit anti-Respiratory Syncytial Virus activity |
title_full |
Serine proteases in neutrophil extracellular traps exhibit anti-Respiratory Syncytial Virus activity |
title_fullStr |
Serine proteases in neutrophil extracellular traps exhibit anti-Respiratory Syncytial Virus activity |
title_full_unstemmed |
Serine proteases in neutrophil extracellular traps exhibit anti-Respiratory Syncytial Virus activity |
title_sort |
Serine proteases in neutrophil extracellular traps exhibit anti-Respiratory Syncytial Virus activity |
author |
Lopes, Bruno Rafael Pereira [UNESP] |
author_facet |
Lopes, Bruno Rafael Pereira [UNESP] da Silva, Gabriel Soares [UNESP] de Lima Menezes, Gabriela de Oliveira, Juliana [UNESP] Watanabe, Aripuanã Sakurada Aranha Porto, Bárbara Nery da Silva, Roosevelt Alves Toledo, Karina Alves [UNESP] |
author_role |
author |
author2 |
da Silva, Gabriel Soares [UNESP] de Lima Menezes, Gabriela de Oliveira, Juliana [UNESP] Watanabe, Aripuanã Sakurada Aranha Porto, Bárbara Nery da Silva, Roosevelt Alves Toledo, Karina Alves [UNESP] |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (UNESP) Universidade Estadual de Londrina (UEL) University of Manitoba Federal University of Jatai Federal University of Juiz de Fora |
dc.contributor.author.fl_str_mv |
Lopes, Bruno Rafael Pereira [UNESP] da Silva, Gabriel Soares [UNESP] de Lima Menezes, Gabriela de Oliveira, Juliana [UNESP] Watanabe, Aripuanã Sakurada Aranha Porto, Bárbara Nery da Silva, Roosevelt Alves Toledo, Karina Alves [UNESP] |
dc.subject.por.fl_str_mv |
Neutrophils Proteases Respiratory syncytial virus Virucidal |
topic |
Neutrophils Proteases Respiratory syncytial virus Virucidal |
description |
Human respiratory syncytial virus (hRSV) is an infectious agent in infants and young children which there are no vaccines or drugs for treatment. Neutrophils are recruited for airway, where they are stimulated by hRSV to release large amounts of neutrophil extracellular traps (NETs). NETs are compound by DNA and proteins, including microbicidal enzymes. They constitute a large part of the mucus accumulated in the lung of patients, compromising their breathing capacity. In contrast, NETs can capture/inactivate hRSV, but the molecules responsible for this effect are unknown. Objectives: We selected microbicidal NET enzymes (elastase, myeloperoxidase, cathepsin-G, and proteinase-3) to assess their anti-hRSV role. Methods and Results: Through in vitro assays using HEp-2 cells, we observed that elastase, proteinase-3, and cathepsin-G, but not myeloperoxidase, showed virucidal effects even at non-cytotoxic concentrations. Elastase and proteinase-3, but not cathepsin-G, cleaved viral F-protein, which is responsible for viral adhesion and fusion with the target cells. Molecular docking analysis indicated the interaction of these macromolecules in the antigenic regions of F-protein through the active regions of the enzymes. Conclusions: Serine proteases from NETs interact and inactive hRSV. These results contribute to the understanding the role of NETs in hRSV infection and to designing treatment strategies for the inflammatory process during respiratory infections. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-04-28T19:50:49Z 2022-04-28T19:50:49Z 2022-05-01 |
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://dx.doi.org/10.1016/j.intimp.2022.108573 International Immunopharmacology, v. 106. 1878-1705 1567-5769 http://hdl.handle.net/11449/223465 10.1016/j.intimp.2022.108573 2-s2.0-85124592170 |
url |
http://dx.doi.org/10.1016/j.intimp.2022.108573 http://hdl.handle.net/11449/223465 |
identifier_str_mv |
International Immunopharmacology, v. 106. 1878-1705 1567-5769 10.1016/j.intimp.2022.108573 2-s2.0-85124592170 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
International Immunopharmacology |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.source.none.fl_str_mv |
Scopus 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 |
|
_version_ |
1799965323636506624 |