Role of neutrophils in CVB3 infection and viral myocarditis

Coxsackievirus B3 (CVB3) is a globally prevalent enterovirus of the Picornaviridae family that is frequently associated with viral myocarditis (VM). Neutrophils, as first responders, may be key cells in determining viral disease outcomes; however, neutrophils have been poorly studied with respect to...

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Autores principales: Rivadeneyra, Leonardo, Charó, Nancy Lorena, Kviatcovsky, Denise, de la Barrera, Silvia Susana, Gómez, Ricardo Martín, Schattner, Mirta Ana
Formato: Articulo Preprint
Lenguaje:Inglés
Publicado: 2018
Materias:
Biología
Ciencias Médicas
CVB3
Enterovirus
Inflammation
Myocarditis
Neutrophils
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/104728
http://hdl.handle.net/11336/94875
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-104728
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Biología
Ciencias Médicas
CVB3
Enterovirus
Inflammation
Myocarditis
Neutrophils
spellingShingle Biología
Ciencias Médicas
CVB3
Enterovirus
Inflammation
Myocarditis
Neutrophils
Rivadeneyra, Leonardo
Charó, Nancy Lorena
Kviatcovsky, Denise
de la Barrera, Silvia Susana
Gómez, Ricardo Martín
Schattner, Mirta Ana
Role of neutrophils in CVB3 infection and viral myocarditis
topic_facet Biología
Ciencias Médicas
CVB3
Enterovirus
Inflammation
Myocarditis
Neutrophils
description Coxsackievirus B3 (CVB3) is a globally prevalent enterovirus of the Picornaviridae family that is frequently associated with viral myocarditis (VM). Neutrophils, as first responders, may be key cells in determining viral disease outcomes; however, neutrophils have been poorly studied with respect to viral infection. Although neutrophils have been ascribed a relevant role in early cardiac inflammation, their precise role in CVB3 infection has not yet been evaluated. In this study, we aimed to determine if the interaction between human neutrophils and CVB3 could lead to viral replication and/or modulation of neutrophil survival and biological functions, and whether neutrophil depletion in a murine model has a beneficial or harmful effect on CVB3 infection. Our results show that CVB3 interacted with but did not replicate in human neutrophils. Neutrophils recognized CVB3 mainly through endosomal TLR-8, and infection triggered NFκB activation. Virus internalization resulted in increased cell survival, up-regulation of CD11b, enhanced adhesion to fibrinogen and fibronectin, and the secretion of IL-6, IL-1β, TNF-α, and IL-8. Supernatants from infected neutrophils exerted chemotactic activity partly mediated by IL-8. The infected neutrophils released myeloperoxidase and triggered neutrophil extracellular trap formation in the presence of TNF-α. In mice infected with CVB3, viral RNA was detected in neutrophils as well as in mononuclear cells. After neutrophil depletion, mice showed reduced VM reflected by a reduction in viral titers, cell exudates, and CCL-2 mRNA levels, as well as the abrogation of reactive cardiomyocyte hypertrophy. Our results indicate that neutrophils have relevant direct and indirect roles in the pathogenesis of CVB3-induced VM.
format Articulo
Preprint
author Rivadeneyra, Leonardo
Charó, Nancy Lorena
Kviatcovsky, Denise
de la Barrera, Silvia Susana
Gómez, Ricardo Martín
Schattner, Mirta Ana
author_facet Rivadeneyra, Leonardo
Charó, Nancy Lorena
Kviatcovsky, Denise
de la Barrera, Silvia Susana
Gómez, Ricardo Martín
Schattner, Mirta Ana
author_sort Rivadeneyra, Leonardo
title Role of neutrophils in CVB3 infection and viral myocarditis
title_short Role of neutrophils in CVB3 infection and viral myocarditis
title_full Role of neutrophils in CVB3 infection and viral myocarditis
title_fullStr Role of neutrophils in CVB3 infection and viral myocarditis
title_full_unstemmed Role of neutrophils in CVB3 infection and viral myocarditis
title_sort role of neutrophils in cvb3 infection and viral myocarditis
publishDate 2018
url http://sedici.unlp.edu.ar/handle/10915/104728
http://hdl.handle.net/11336/94875
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