Neutrophil extracellular traps possess anti-human respiratory syncytial virus activity: Possible interaction with the viral F protein

Detalhes bibliográficos
Autor(a) principal: Souza, Priscila Silva Sampaio [UNESP]
Data de Publicação: 2018
Outros Autores: 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]
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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spelling 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/openAccess2023-12-19T06:26:50Zoai:repositorio.unesp.br:11449/176304Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462023-12-19T06:26:50Repositório 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
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