| Author | Teixeira, Gabrielly Sbano | |
| Author | Andrade, Audrien Alves | |
| Author | Torres, Lauana Ribas | |
| Author | Lima, Dinair Couto | |
| Author | Moreira, Otacilio C. | |
| Author | Abreu, Rayane da Silva | |
| Author | Waghabi, Mariana Caldas | |
| Author | Souza, Elen Mello de | |
| Access date | 2022-06-13T11:23:16Z | |
| Available date | 2022-06-13T11:23:16Z | |
| Document date | 2022 | |
| Citation | TEIXEIRA, Gabrielly Sbano et al. Suppression of TGF‐β/Smad2 signaling by GW788388 enhances DENV‐2 clearance in macrophages. Journal of Medical Virology, p. 1 - 10, May 2022. | pt_BR |
| ISSN | 1096-9071 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/53217 | |
| Language | eng | pt_BR |
| Publisher | Wiley | pt_BR |
| Rights | open access | |
| Subject in Portuguese | Vírus da Dengue | pt_BR |
| Subject in Portuguese | Macrófagos | pt_BR |
| Subject in Portuguese | Sinalização clássica de TGF-β1 | pt_BR |
| Subject in Portuguese | Inibidor do receptor de TGFβ | pt_BR |
| Title | Suppression of TGF‐β/Smad2 signaling by GW788388 enhances DENV‐2 clearance in macrophages | pt_BR |
| Type | Article | |
| DOI | 10.1002/jmv.27879 | |
| Abstract | Dengue fever, caused by the dengue virus (DENV‐1, −2, −3, and −4), affects millions of
people in the tropical and subtropical regions worldwide. Severe dengue is correlated
with high viraemia and cytokine storm, such as high levels of transforming growth
factor‐β1 (TGF‐β1) in the patient's serum. Here, the TGF‐β1 signaling was investigated
in the context of in vitro viral clearance. Macrophages were infected with DENV‐2 at
MOI 5 and treated with the TGF‐β receptor 1 and 2 inhibitor, GW788388. TGF‐β1
expression, signal transduction and viral load were evaluated 48 h after DENV‐2
infection by enzyme‐linked immunoassay, immunofluorescence, and RT‐qPCR assays.
Total TGF‐β1 levelwas reduced in 15%afterDENV‐2 infection, but the secretion of its
biologically active form increased threefold during infection, which was followed by the
phosphorylation of Smad2 protein. Phosphorylation of Smad2 was reduced by
treatment with GW788388 and it was correlated with reduced cytokine production.
Importantly, treatment led to a dose‐dependent reduction in viral load, ranging from
6.6×105 RNA copies/ml in untreated cultures to 2.3 × 103 RNA copies/ml in cultures
treated with 2 ng/ml of GW788388. The anti‐TGF‐β1 antibody treatment also induced
a significant reduction in viral load to 1.6 × 103 RNA copies/ml. On the other hand, the
addition of recombinant TGF‐β1 in infected cultures promoted an increase in viral load
to 7.0 × 106 RNA copies/ml. These results support that TGF‐β1 plays a significant role
in DENV‐2 replication into macrophages and suggest that targeting TGF‐β1 may
represent an alternative therapeutic strategy to be explored in dengue infection. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Morfologia e Morfogênese Viral. Rio de Janeiro, Rio de Janeiro, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Virologia Molecular. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Virologia Molecular. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Mosquitos Transmissores de Hematozoários. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Plataforma de PCR em Tempo Real RPT09A, Laboratório de Biologia Molecular e Doenças Endêmicas, Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genômica Funcional e Bioinformática. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genômica Funcional e Bioinformática. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Morfologia e Morfogênese Viral. Rio de Janeiro, Rio de Janeiro, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Virologia Molecular. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Subject | Classical TGF‐β1 signaling | pt_BR |
| Subject | Dengue virus | pt_BR |
| Subject | GW788388 | pt_BR |
| Subject | Macrophages | pt_BR |
| Subject | TGFβ receptor inhibitor | pt_BR |
| Subject | TGF‐β1 | pt_BR |
