Serine proteases in neutrophil extracellular traps exhibit anti-Respiratory Syncytial Virus activity.

Autor: Lopes BRP; São Paulo State University (UNESP), Institute of Biosciences, Humanities and Exact Sciences, São José do Rio Preto - SP, Brazil., da Silva GS; São Paulo State University (UNESP), School of Sciences, Humanities and Languages, Assis, Brazil., de Lima Menezes G; Biosystems Collaborative Nucleus, Institute of Exact Sciences, Federal University of Jatai, Jatai-GO, Brazil., de Oliveira J; São Paulo State University (UNESP), School of Sciences, Humanities and Languages, Assis, Brazil; Graduate Program in Applied and Computational Mathematics - PGMAC - State University of Londrina, Londrina-PR, Brazil., Watanabe ASA; Virology Laboratory, Center for Microbiology Studies, Department of Parasitology, Microbiology and Immunology, Federal University of Juiz de Fora, Juiz de Fora, Minas Gerais, Brazil., Porto BN; Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, Canada., da Silva RA; Biosystems Collaborative Nucleus, Institute of Exact Sciences, Federal University of Jatai, Jatai-GO, Brazil., Toledo KA; São Paulo State University (UNESP), Institute of Biosciences, Humanities and Exact Sciences, São José do Rio Preto - SP, Brazil; São Paulo State University (UNESP), School of Sciences, Humanities and Languages, Assis, Brazil. Electronic address: karina.toledo@unesp.br.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2022 May; Vol. 106, pp. 108573. Date of Electronic Publication: 2022 Feb 16.
DOI: 10.1016/j.intimp.2022.108573
Abstrakt: 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.
(Copyright © 2022. Published by Elsevier B.V.)
Databáze: MEDLINE
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