| Author | Teixeira, Anna Cecillia Quirino | |
| Author | Rozini, Stephane Vicente | |
| Author | Lima, Giselle Barbosa | |
| Author | Coelho, Diego Rodrigues | |
| Author | Carneiro, Pedro Henrique | |
| Author | Borges, Ronaldo Mohana | |
| Author | Bozza, Patrícia T. | |
| Author | Hottz, Eugenio D. | |
| Access date | 2020-07-31T18:51:54Z | |
| Available date | 2020-07-31T18:51:54Z | |
| Document date | 2020 | |
| Citation | QUIRINO-TEIXEIRA, Anna Cecilia et al. Inflammatory signaling in dengue-infected platelets requires translation and secretion of nonstructural protein 1. Blood Advances, v. 4, n. 9, p. 2018-2031, May 2020. | pt_BR |
| ISSN | 2473-9529 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/42492 | |
| Language | eng | pt_BR |
| Publisher | American Society of Hematology: | pt_BR |
| Rights | open access | |
| Subject in Portuguese | Sinalização inflamatória | pt_BR |
| Subject in Portuguese | Plaquetas | pt_BR |
| Subject in Portuguese | Infecção | pt_BR |
| Subject in Portuguese | Dengue | pt_BR |
| Subject in Portuguese | Proteína não estrutural 1 | pt_BR |
| Title | Inflammatory signaling in dengue-infected platelets requires translation and secretion of nonstructural protein 1 | pt_BR |
| Type | Article | |
| DOI | 10.1182/bloodadvances.2019001169 | |
| Abstract | Emerging evidence identifies major contributions of platelets to inflammatory amplification
in dengue, but the mechanisms of infection-driven platelet activation are not completely
understood. Dengue virus nonstructural protein-1 (DENV NS1) is a viral protein secreted by
infected cells with recognized roles in dengue pathogenesis, but it remains unknown
whether NS1 contributes to the inflammatory phenotype of infected platelets. This study
shows that recombinant DENV NS1 activated platelets toward an inflammatory phenotype
that partially reproduced DENV infection. NS1 stimulation induced translocation of
a-granules and release of stored factors, but not of newly synthesized interleukin-1b (IL-1b).
Even though both NS1 and DENV were able to induce pro-IL-1b synthesis, only DENV
infection triggered caspase-1 activation and IL-1b release by platelets. A more complete
thromboinflammatory phenotype was achieved by synergistic activation of NS1 with classic
platelet agonists, enhancing a-granule translocation and inducing thromboxane A2
synthesis (thrombin and platelet-activating factor), or activating caspase-1 for IL-1b
processing and secretion (adenosine triphosphate). Also, platelet activation by NS1 partially
depended on toll-like receptor-4 (TLR-4), but not TLR-2/6. Finally, the platelets sustained viral
genome translation and replication, but did not support the release of viral progeny to the
extracellular milieu, characterizing an abortive viral infection. Although DENV infection
was not productive, translation of the DENV genome led to NS1 expression and release by
platelets, contributing to the activation of infected platelets through an autocrine loop. These
data reveal distinct, new mechanisms for platelet activation in dengue, involving DENV
genome translation and NS1-induced platelet activation via platelet TLR4. | pt_BR |
| Affilliation | Universidade Federal de Juiz de Fora. Departamento de Bioquímica. Laboratório de Análise de Glicoconjugates. Laboratório de Imunotrombose. Juiz de Fora, MG, Brasil / Universidade Federal de Juiz de Fora. Departamento de Bioquímica. Laboratório de Análises de Glicoconjugates. Juiz de Fora, MG, Brasil. | pt_BR |
| Affilliation | Universidade Federal de Juiz de Fora. Departamento de Bioquímica. Laboratório de Análise de Glicoconjugates. Laboratório de Imunotrombose. Juiz de Fora, MG, Brasil / Universidade Federal de Juiz de Fora. Departamento de Bioquímica. Laboratório de Análises de Glicoconjugates. Juiz de Fora, MG, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. 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 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 | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal de Juiz de Fora. Departamento de Bioquímica. Laboratório de Análise de Glicoconjugates. Laboratório de Imunotrombose. Juiz de Fora, MG, Brasil / Universidade Federal de Juiz de Fora. Departamento de Bioquímica. Laboratório de Análises de Glicoconjugates. Juiz de Fora, MG, Brasil. | pt_BR |
| Subject | inflammatory signaling | pt_BR |
| Subject | Platelets | pt_BR |
| Subject | Infection | pt_BR |
| Subject | Nonstructural protein 1 | pt_BR |
| Subject | Dengue | pt_BR |
