Contact System Activation in Plasma from Dengue Patients Might Harness Endothelial Virus Replication through the Signaling of Bradykinin Receptors
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2021 |
| Outros Autores: | , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/46493 |
Resumo: | Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Departamento de Virologia. Rio de Janeiro, RJ, Brasil. |
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Coelho, Sharton V. A.Rusr, Naiara M.Vellasco, LucasPapa, Michelle P.Pereira, Aline S. G.Palazzo, Matheus Ferreira da SilvaJuliano, Maria AparecidaCosta, Simone M.Alves, Ada M. B.Cordeiro, Marli T.Marques, Ernesto T. A.Scharfstein, JúlioArruda, Luciana B. de2021-04-02T20:09:58Z2021-04-02T20:09:58Z2021COELHO, Sharton V. A. et al. Contact System Activation in Plasma from Dengue Patients Might Harness Endothelial Virus Replication through the Signaling of Bradykinin Receptors. Pharmaceuticals, v. 14, n. 56, p. 1-27, 2021.1424-8247https://www.arca.fiocruz.br/handle/icict/4649310.3390/ph14010056engMDPIDengueBradykininCélulas endoteliaisCaminho de contatoBradykinin receptor B2Sistema Kallikrein-kininDengueBradykininEndothelial cellsKallikrein-kinin systemContact pathwayBradykinin receptor B2Contact System Activation in Plasma from Dengue Patients Might Harness Endothelial Virus Replication through the Signaling of Bradykinin Receptorsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Departamento de Virologia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Departamento de Virologia. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Departamento de Virologia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Departamento de Virologia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.Universidade Federal de São Paulo. Escola Paulista de Medicina. Departamento de Biofísica. São Paulo, SP, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biotecnologia e Fisiologia de Infecções Virais. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biotecnologia e Fisiologia de Infecções Virais. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil.Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil / University of Pittsburgh. Department of Infectious Diseases. Pittsburgh. PA, USA.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Departamento de Virologia. Rio de Janeiro, RJ, Brasil.Abstract: Since exacerbated inflammation and microvascular leakage are hallmarks of dengue virus (DENV) infection, here we interrogated whether systemic activation of the contact/kallikrein-kinin system (KKS) might hamper endothelial function. In vitro assays showed that dextran sulfate, a potent contact activator, failed to generate appreciable levels of activated plasma kallikrein (PKa) in the large majority of samples from a dengue cohort (n = 70), irrespective of severity of clinical symptoms. Impaired formation of PKa in dengue-plasmas correlated with the presence of cleaved Factor XII and high molecular weight kininogen (HK), suggesting that the prothrombogenic contact system is frequently triggered during the course of infection. Using two pathogenic arboviruses, DENV or Zika virus (ZIKV), we then asked whether exogenous BK could influence the outcome of infection of human brain microvascular endothelial cells (HBMECs). Unlike the unresponsive phenotype of Zika-infected HBMECs, we found that BK, acting via B2R, vigorously stimulated DENV-2 replication by reverting nitric oxide-driven apoptosis of endothelial cells. Using the mouse model of cerebral dengue infection, we next demonstrated that B2R targeting by icatibant decreased viral load in brain tissues. In summary, our study suggests that contact/KKS activation followed by BK-induced enhancement of DENV replication in the endothelium may underlie microvascular pathology in dengue.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/46493/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALSimoneCosta_AdaAlves_etal_IOC_2021.pdfSimoneCosta_AdaAlves_etal_IOC_2021.pdfapplication/pdf8140978https://www.arca.fiocruz.br/bitstream/icict/46493/2/SimoneCosta_AdaAlves_etal_IOC_2021.pdf1aee128bab2327434e773aec58de2bb2MD52TEXTSimoneCosta_AdaAlves_etal_IOC_2021.pdf.txtSimoneCosta_AdaAlves_etal_IOC_2021.pdf.txtExtracted texttext/plain96055https://www.arca.fiocruz.br/bitstream/icict/46493/3/SimoneCosta_AdaAlves_etal_IOC_2021.pdf.txt6b401a993fd2c98fc4f8a03eb7c75938MD53icict/464932021-05-22 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| dc.title.pt_BR.fl_str_mv |
Contact System Activation in Plasma from Dengue Patients Might Harness Endothelial Virus Replication through the Signaling of Bradykinin Receptors |
| title |
Contact System Activation in Plasma from Dengue Patients Might Harness Endothelial Virus Replication through the Signaling of Bradykinin Receptors |
| spellingShingle |
Contact System Activation in Plasma from Dengue Patients Might Harness Endothelial Virus Replication through the Signaling of Bradykinin Receptors Coelho, Sharton V. A. Dengue Bradykinin Células endoteliais Caminho de contato Bradykinin receptor B2 Sistema Kallikrein-kinin Dengue Bradykinin Endothelial cells Kallikrein-kinin system Contact pathway Bradykinin receptor B2 |
| title_short |
Contact System Activation in Plasma from Dengue Patients Might Harness Endothelial Virus Replication through the Signaling of Bradykinin Receptors |
| title_full |
Contact System Activation in Plasma from Dengue Patients Might Harness Endothelial Virus Replication through the Signaling of Bradykinin Receptors |
| title_fullStr |
Contact System Activation in Plasma from Dengue Patients Might Harness Endothelial Virus Replication through the Signaling of Bradykinin Receptors |
| title_full_unstemmed |
Contact System Activation in Plasma from Dengue Patients Might Harness Endothelial Virus Replication through the Signaling of Bradykinin Receptors |
| title_sort |
Contact System Activation in Plasma from Dengue Patients Might Harness Endothelial Virus Replication through the Signaling of Bradykinin Receptors |
| author |
Coelho, Sharton V. A. |
| author_facet |
Coelho, Sharton V. A. Rusr, Naiara M. Vellasco, Lucas Papa, Michelle P. Pereira, Aline S. G. Palazzo, Matheus Ferreira da Silva Juliano, Maria Aparecida Costa, Simone M. Alves, Ada M. B. Cordeiro, Marli T. Marques, Ernesto T. A. Scharfstein, Júlio Arruda, Luciana B. de |
| author_role |
author |
| author2 |
Rusr, Naiara M. Vellasco, Lucas Papa, Michelle P. Pereira, Aline S. G. Palazzo, Matheus Ferreira da Silva Juliano, Maria Aparecida Costa, Simone M. Alves, Ada M. B. Cordeiro, Marli T. Marques, Ernesto T. A. Scharfstein, Júlio Arruda, Luciana B. de |
| author2_role |
author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Coelho, Sharton V. A. Rusr, Naiara M. Vellasco, Lucas Papa, Michelle P. Pereira, Aline S. G. Palazzo, Matheus Ferreira da Silva Juliano, Maria Aparecida Costa, Simone M. Alves, Ada M. B. Cordeiro, Marli T. Marques, Ernesto T. A. Scharfstein, Júlio Arruda, Luciana B. de |
| dc.subject.other.pt_BR.fl_str_mv |
Dengue Bradykinin Células endoteliais Caminho de contato Bradykinin receptor B2 Sistema Kallikrein-kinin |
| topic |
Dengue Bradykinin Células endoteliais Caminho de contato Bradykinin receptor B2 Sistema Kallikrein-kinin Dengue Bradykinin Endothelial cells Kallikrein-kinin system Contact pathway Bradykinin receptor B2 |
| dc.subject.en.pt_BR.fl_str_mv |
Dengue Bradykinin Endothelial cells Kallikrein-kinin system Contact pathway Bradykinin receptor B2 |
| description |
Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Departamento de Virologia. Rio de Janeiro, RJ, Brasil. |
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2021 |
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2021-04-02T20:09:58Z |
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2021-04-02T20:09:58Z |
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2021 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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COELHO, Sharton V. A. et al. Contact System Activation in Plasma from Dengue Patients Might Harness Endothelial Virus Replication through the Signaling of Bradykinin Receptors. Pharmaceuticals, v. 14, n. 56, p. 1-27, 2021. |
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https://www.arca.fiocruz.br/handle/icict/46493 |
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1424-8247 |
| dc.identifier.doi.none.fl_str_mv |
10.3390/ph14010056 |
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COELHO, Sharton V. A. et al. Contact System Activation in Plasma from Dengue Patients Might Harness Endothelial Virus Replication through the Signaling of Bradykinin Receptors. Pharmaceuticals, v. 14, n. 56, p. 1-27, 2021. 1424-8247 10.3390/ph14010056 |
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