| Author | Coelho, Sharton V. A. | |
| Author | Rusr, Naiara M. | |
| Author | Vellasco, Lucas | |
| Author | Papa, Michelle P. | |
| Author | Pereira, Aline S. G. | |
| Author | Palazzo, Matheus Ferreira da Silva | |
| Author | Juliano, Maria Aparecida | |
| Author | Costa, Simone M. | |
| Author | Alves, Ada M. B. | |
| Author | Cordeiro, Marli T. | |
| Author | Marques, Ernesto T. A. | |
| Author | Scharfstein, Júlio | |
| Author | Arruda, Luciana B. de | |
| Access date | 2021-04-02T20:09:58Z | |
| Available date | 2021-04-02T20:09:58Z | |
| Document date | 2021 | |
| Citation | 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. | pt_BR |
| ISSN | 1424-8247 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/46493 | |
| Language | eng | pt_BR |
| Publisher | MDPI | pt_BR |
| Rights | open access | |
| Subject in Portuguese | Dengue | pt_BR |
| Subject in Portuguese | Bradykinin | pt_BR |
| Subject in Portuguese | Células endoteliais | pt_BR |
| Subject in Portuguese | Caminho de contato | pt_BR |
| Subject in Portuguese | Bradykinin receptor B2 | pt_BR |
| Subject in Portuguese | Sistema Kallikrein-kinin | pt_BR |
| Title | Contact System Activation in Plasma from Dengue Patients Might Harness Endothelial Virus Replication through the Signaling of Bradykinin Receptors | pt_BR |
| Type | Article | |
| DOI | 10.3390/ph14010056 | |
| Abstract | 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. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Departamento de Virologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | 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. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Departamento de Virologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Departamento de Virologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal de São Paulo. Escola Paulista de Medicina. Departamento de Biofísica. São Paulo, SP, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biotecnologia e Fisiologia de Infecções Virais. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biotecnologia e Fisiologia de Infecções Virais. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil / University of Pittsburgh. Department of Infectious Diseases. Pittsburgh. PA, USA. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Departamento de Virologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Subject | Dengue | pt_BR |
| Subject | Bradykinin | pt_BR |
| Subject | Endothelial cells | pt_BR |
| Subject | Kallikrein-kinin system | pt_BR |
| Subject | Contact pathway | pt_BR |
| Subject | Bradykinin receptor B2 | pt_BR |
