Cell-to-cell spread of vaccinia virus is promoted by TGF-ß-independent Smad4 signalling.
Cell Microbiol
; 22(8): e13206, 2020 08.
Article
en En
| MEDLINE
| ID: mdl-32237038
ABSTRACT
The induction of Smad signalling by the extracellular ligand TGF-ß promotes tissue plasticity and cell migration in developmental and pathological contexts. Here, we show that vaccinia virus (VACV) stimulates the activity of Smad transcription factors and expression of TGF-ß/Smad-responsive genes at the transcript and protein levels. Accordingly, infected cells share characteristics to those undergoing TGF-ß/Smad-mediated epithelial-to-mesenchymal transition (EMT). Depletion of the Smad4 protein, a common mediator of TGF-ß signalling, results in an attenuation of viral cell-to-cell spread and reduced motility of infected cells. VACV induction of TGF-ß/Smad-responsive gene expression does not require the TGF-ß ligand or type I and type II TGF-ß receptors, suggesting a novel, non-canonical Smad signalling pathway. Additionally, the spread of ectromelia virus, a related orthopoxvirus that does not activate a TGF-ß/Smad response, is enhanced by the addition of exogenous TGF-ß. Together, our results indicate that VACV orchestrates a TGF-ß-like response via a unique activation mechanism to enhance cell migration and promote virus spread.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Virus Vaccinia
/
Transducción de Señal
/
Factor de Crecimiento Transformador beta
/
Proteína Smad4
Límite:
Humans
Idioma:
En
Revista:
Cell Microbiol
Asunto de la revista:
MICROBIOLOGIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Australia