Neutrophil extracellular traps possess anti-human respiratory syncytial virus activity: Possible interaction with the viral F protein
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1016/j.virusres.2018.04.001 http://hdl.handle.net/11449/176304 |
Resumo: | Human respiratory syncytial virus (hRSV) is one of the main etiological agents of diseases of the lower respiratory tract, and is often responsible for the hospitalization of children and the elderly. To date, treatments are only palliative and there is no vaccine available. The airways of patients infected with hRSV exhibit intense neutrophil infiltration, which is responsible for the release of neutrophil extracellular traps (NETs). These are extracellular structures consisting of DNA associated with intracellular proteins, and are efficient in capturing and eliminating various microorganisms, including some viruses. hRSV induces the release of NETs into the lung tissue of infected individuals; however, the pathophysiological consequences of this event have not been elucidated. The objective of this study was to utilize in vitro and in silico assays to investigate the impact of NETs on hRSV infection. NETs, generated by neutrophils stimulated with phorbol myristate acetate (PMA), displayed long fragments of DNA and an electrophoretic profile suggestive of the presence of proteins that are classically associated with these structures (elastase, cathepsin G, myeloperoxidase, and histones). The presence of NETs (>2 μg/ml) in HEp-2 cell culture medium resulted in cellular cytotoxicity of less than 50%. Pre-incubation (1 h) of viral particles (multiplicity of infection (MOI) values of 0.1, 0.5, and 1.0) with NETs (2–32 μg/ml) resulted in cellular protection from virus-induced death of HEp-2 cells. Concurrently, there was a reduction in the formation of syncytia, which is related to decreased viral spread in infected tissue. Results from western blotting and molecular docking, suggest interactions between F protein of the hRSV viral envelope and BPI (bactericidal permeability-increasing protein), a microbicidal member of NETs. Interactions occurred at sites important for the neutralization and coordination of the hRSV infection/replication process. Our results showed that the presence of NETs decreases hRSV-induced cellular damage, possibly by directly affecting viral particle capture and/or interfering with the fusion activity of the F protein. These findings broaden the understanding of the role of NETs during hRSV infection. |
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Neutrophil extracellular traps possess anti-human respiratory syncytial virus activity: Possible interaction with the viral F proteinMolecular dockingNeutrophil extracellular trapsRespiratory syncytial virusHuman respiratory syncytial virus (hRSV) is one of the main etiological agents of diseases of the lower respiratory tract, and is often responsible for the hospitalization of children and the elderly. To date, treatments are only palliative and there is no vaccine available. The airways of patients infected with hRSV exhibit intense neutrophil infiltration, which is responsible for the release of neutrophil extracellular traps (NETs). These are extracellular structures consisting of DNA associated with intracellular proteins, and are efficient in capturing and eliminating various microorganisms, including some viruses. hRSV induces the release of NETs into the lung tissue of infected individuals; however, the pathophysiological consequences of this event have not been elucidated. The objective of this study was to utilize in vitro and in silico assays to investigate the impact of NETs on hRSV infection. NETs, generated by neutrophils stimulated with phorbol myristate acetate (PMA), displayed long fragments of DNA and an electrophoretic profile suggestive of the presence of proteins that are classically associated with these structures (elastase, cathepsin G, myeloperoxidase, and histones). The presence of NETs (>2 μg/ml) in HEp-2 cell culture medium resulted in cellular cytotoxicity of less than 50%. Pre-incubation (1 h) of viral particles (multiplicity of infection (MOI) values of 0.1, 0.5, and 1.0) with NETs (2–32 μg/ml) resulted in cellular protection from virus-induced death of HEp-2 cells. Concurrently, there was a reduction in the formation of syncytia, which is related to decreased viral spread in infected tissue. Results from western blotting and molecular docking, suggest interactions between F protein of the hRSV viral envelope and BPI (bactericidal permeability-increasing protein), a microbicidal member of NETs. Interactions occurred at sites important for the neutralization and coordination of the hRSV infection/replication process. Our results showed that the presence of NETs decreases hRSV-induced cellular damage, possibly by directly affecting viral particle capture and/or interfering with the fusion activity of the F protein. These findings broaden the understanding of the role of NETs during hRSV infection.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Department of Biological Sciences Universidade Estadual Paulista – UNESP (FCLAssis)Department of Physics Universidade Estadual Paulista – UNESP (IBILCE São José do Rio Preto)Centro Multiusuário de Inovação Biomolecular (CMIB) Universidade Estadual Paulista – UNESP (IBILCE São José do Rio Preto)Department of Biological Sciences Universidade Estadual Paulista – UNESP (FCLAssis)Department of Physics Universidade Estadual Paulista – UNESP (IBILCE São José do Rio Preto)Centro Multiusuário de Inovação Biomolecular (CMIB) Universidade Estadual Paulista – UNESP (IBILCE São José do Rio Preto)CAPES: 2016/03867-3Universidade Estadual Paulista (Unesp)Souza, Priscila Silva Sampaio [UNESP]Barbosa, Lia Vezenfard [UNESP]Diniz, Larissa Figueiredo Alves [UNESP]da Silva, Gabriel Soares [UNESP]Lopes, Bruno Rafael Pereira [UNESP]Souza, Pedro Miyadaira Ribeiro [UNESP]de Araujo, Gabriela Campos [UNESP]Pessoa, Diogo [UNESP]de Oliveira, Juliana [UNESP]Souza, Fátima Pereira [UNESP]Toledo, Karina Alves [UNESP]2018-12-11T17:20:01Z2018-12-11T17:20:01Z2018-06-02info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article68-77application/pdfhttp://dx.doi.org/10.1016/j.virusres.2018.04.001Virus Research, v. 251, p. 68-77.1872-74920168-1702http://hdl.handle.net/11449/17630410.1016/j.virusres.2018.04.0012-s2.0-850467675062-s2.0-85046767506.pdfScopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengVirus Research1,147info:eu-repo/semantics/openAccess2024-10-29T13:10:46Zoai:repositorio.unesp.br:11449/176304Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestrepositoriounesp@unesp.bropendoar:29462024-10-29T13:10:46Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Neutrophil extracellular traps possess anti-human respiratory syncytial virus activity: Possible interaction with the viral F protein |
title |
Neutrophil extracellular traps possess anti-human respiratory syncytial virus activity: Possible interaction with the viral F protein |
spellingShingle |
Neutrophil extracellular traps possess anti-human respiratory syncytial virus activity: Possible interaction with the viral F protein Souza, Priscila Silva Sampaio [UNESP] Molecular docking Neutrophil extracellular traps Respiratory syncytial virus |
title_short |
Neutrophil extracellular traps possess anti-human respiratory syncytial virus activity: Possible interaction with the viral F protein |
title_full |
Neutrophil extracellular traps possess anti-human respiratory syncytial virus activity: Possible interaction with the viral F protein |
title_fullStr |
Neutrophil extracellular traps possess anti-human respiratory syncytial virus activity: Possible interaction with the viral F protein |
title_full_unstemmed |
Neutrophil extracellular traps possess anti-human respiratory syncytial virus activity: Possible interaction with the viral F protein |
title_sort |
Neutrophil extracellular traps possess anti-human respiratory syncytial virus activity: Possible interaction with the viral F protein |
author |
Souza, Priscila Silva Sampaio [UNESP] |
author_facet |
Souza, Priscila Silva Sampaio [UNESP] Barbosa, Lia Vezenfard [UNESP] Diniz, Larissa Figueiredo Alves [UNESP] da Silva, Gabriel Soares [UNESP] Lopes, Bruno Rafael Pereira [UNESP] Souza, Pedro Miyadaira Ribeiro [UNESP] de Araujo, Gabriela Campos [UNESP] Pessoa, Diogo [UNESP] de Oliveira, Juliana [UNESP] Souza, Fátima Pereira [UNESP] Toledo, Karina Alves [UNESP] |
author_role |
author |
author2 |
Barbosa, Lia Vezenfard [UNESP] Diniz, Larissa Figueiredo Alves [UNESP] da Silva, Gabriel Soares [UNESP] Lopes, Bruno Rafael Pereira [UNESP] Souza, Pedro Miyadaira Ribeiro [UNESP] de Araujo, Gabriela Campos [UNESP] Pessoa, Diogo [UNESP] de Oliveira, Juliana [UNESP] Souza, Fátima Pereira [UNESP] Toledo, Karina Alves [UNESP] |
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 |
Souza, Priscila Silva Sampaio [UNESP] Barbosa, Lia Vezenfard [UNESP] Diniz, Larissa Figueiredo Alves [UNESP] da Silva, Gabriel Soares [UNESP] Lopes, Bruno Rafael Pereira [UNESP] Souza, Pedro Miyadaira Ribeiro [UNESP] de Araujo, Gabriela Campos [UNESP] Pessoa, Diogo [UNESP] de Oliveira, Juliana [UNESP] Souza, Fátima Pereira [UNESP] Toledo, Karina Alves [UNESP] |
dc.subject.por.fl_str_mv |
Molecular docking Neutrophil extracellular traps Respiratory syncytial virus |
topic |
Molecular docking Neutrophil extracellular traps Respiratory syncytial virus |
description |
Human respiratory syncytial virus (hRSV) is one of the main etiological agents of diseases of the lower respiratory tract, and is often responsible for the hospitalization of children and the elderly. To date, treatments are only palliative and there is no vaccine available. The airways of patients infected with hRSV exhibit intense neutrophil infiltration, which is responsible for the release of neutrophil extracellular traps (NETs). These are extracellular structures consisting of DNA associated with intracellular proteins, and are efficient in capturing and eliminating various microorganisms, including some viruses. hRSV induces the release of NETs into the lung tissue of infected individuals; however, the pathophysiological consequences of this event have not been elucidated. The objective of this study was to utilize in vitro and in silico assays to investigate the impact of NETs on hRSV infection. NETs, generated by neutrophils stimulated with phorbol myristate acetate (PMA), displayed long fragments of DNA and an electrophoretic profile suggestive of the presence of proteins that are classically associated with these structures (elastase, cathepsin G, myeloperoxidase, and histones). The presence of NETs (>2 μg/ml) in HEp-2 cell culture medium resulted in cellular cytotoxicity of less than 50%. Pre-incubation (1 h) of viral particles (multiplicity of infection (MOI) values of 0.1, 0.5, and 1.0) with NETs (2–32 μg/ml) resulted in cellular protection from virus-induced death of HEp-2 cells. Concurrently, there was a reduction in the formation of syncytia, which is related to decreased viral spread in infected tissue. Results from western blotting and molecular docking, suggest interactions between F protein of the hRSV viral envelope and BPI (bactericidal permeability-increasing protein), a microbicidal member of NETs. Interactions occurred at sites important for the neutralization and coordination of the hRSV infection/replication process. Our results showed that the presence of NETs decreases hRSV-induced cellular damage, possibly by directly affecting viral particle capture and/or interfering with the fusion activity of the F protein. These findings broaden the understanding of the role of NETs during hRSV infection. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018-12-11T17:20:01Z 2018-12-11T17:20:01Z 2018-06-02 |
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.virusres.2018.04.001 Virus Research, v. 251, p. 68-77. 1872-7492 0168-1702 http://hdl.handle.net/11449/176304 10.1016/j.virusres.2018.04.001 2-s2.0-85046767506 2-s2.0-85046767506.pdf |
url |
http://dx.doi.org/10.1016/j.virusres.2018.04.001 http://hdl.handle.net/11449/176304 |
identifier_str_mv |
Virus Research, v. 251, p. 68-77. 1872-7492 0168-1702 10.1016/j.virusres.2018.04.001 2-s2.0-85046767506 2-s2.0-85046767506.pdf |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Virus Research 1,147 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
68-77 application/pdf |
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 |
repositoriounesp@unesp.br |
_version_ |
1826304313127862272 |