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

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Sampaio Souza, Priscila Silva [1] ; Barbosa, Lia Vezenfard [1] ; Alves Diniz, Larissa Figueiredo [1] ; da Silva, Gabriel Soares [1] ; Pereira Lopes, Bruno Rafael [1] ; Ribeiro Souza, Pedro Miyadaira [1] ; de Araujo, Gabriela Campos [2, 3] ; Pessoa, Diogo [1] ; de Oliveira, Juliana [1] ; Souza, Fatima Pereira [2, 3] ; Toledo, Karina Alves [1]
Número total de Autores: 11
Afiliação do(s) autor(es):
[1] Univ Estadual Paulista UNESP FCLAssis, Dept Biol Sci, Sao Paulo - Brazil
[2] Univ Estadual Paulista UNESP IBILCE, Dept Phys, Sao Jose Do Rio Preto - Brazil
[3] Univ Estadual Paulista UNESP IBILCE, CMIB, Sao Jose Do Rio Preto - Brazil
Número total de Afiliações: 3
Tipo de documento: Artigo Científico
Fonte: VIRUS RESEARCH; v. 251, p. 68-77, JUN 2 2018.
Citações Web of Science: 2

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 mu/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 mu g/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. (AU)

Processo FAPESP: 16/03867-3 - Efeito das redes extracelulares dos neutrófilos (NETs) no bloqueio da replicação do vírus sincicial respiratório humano (HRSV)
Beneficiário:Karina Alves de Toledo
Modalidade de apoio: Auxílio à Pesquisa - Regular