| dc.contributor |
Ministerio de Educación y Ciencia (España) |
|
| dc.contributor |
Wellcome Trust |
|
| dc.contributor |
Fundación Ramón Areces |
|
| dc.creator |
Granja, Aitor G. |
|
| dc.creator |
Nogal París, María Luisa |
|
| dc.creator |
Hurtado, Carolina |
|
| dc.creator |
Aguila, Carmen del |
|
| dc.creator |
Carrascosa, Ángel L. |
|
| dc.creator |
Salas, María Luisa |
|
| dc.creator |
Fresno, Manuel |
|
| dc.creator |
Revilla Novella, Yolanda |
|
| dc.date |
2008-06-09T14:13:57Z |
|
| dc.date |
2008-06-09T14:13:57Z |
|
| dc.date |
2006-01 |
|
| dc.date.accessioned |
2017-01-31T01:37:10Z |
|
| dc.date.available |
2017-01-31T01:37:10Z |
|
| dc.identifier |
The Journal of Immunology, 2006, 176: 451-462 |
|
| dc.identifier |
0022-1767 (Print) |
|
| dc.identifier |
1550-6606 (Online) |
|
| dc.identifier |
http://hdl.handle.net/10261/4921 |
|
| dc.identifier.uri |
http://dspace.mediu.edu.my:8181/xmlui/handle/10261/4921 |
|
| dc.description |
Article available at http://www.jimmunol.org/cgi/content/abstract/176/1/451 |
|
| dc.description |
African swine fever virus (ASFV) is able to inhibit TNF--induced gene expression through the synthesis of A238L protein. This was shown by the use of deletion mutants lacking the A238L gene from the Vero cell-adapted Ba71V ASFV strain and from the virulent isolate E70. To further analyze the molecular mechanism by which the viral gene controls TNF-, we have used Jurkat cells stably transfected with the viral gene to identify the TNF- regulatory elements involved in the induction of the gene after stimulation with PMA and calcium ionophore. We have thus identified the cAMP-responsive element and 3 sites on the TNF- promoter as the responsible of the gene activation, and demonstrate that A238L inhibits TNF- expression through these DNA binding sites. This inhibition was partially reverted by overexpression of the transcriptional factors NF-AT, NF-B, and c-Jun. Furthermore, we present evidence that A238L inhibits the activation of TNF- by modulating NF-B, NF-AT, and c-Jun trans activation through a mechanism that involves CREB binding protein/p300 function, because overexpression of these transcriptional coactivators recovers TNF- promoter activity. In addition, we show that A238L is a nuclear protein that binds to the cyclic AMP-responsive element/3 complex, thus displacing the CREB binding protein/p300 coactivators. Taken together, these results establish a novel mechanism in the control of TNF- gene expression by a viral protein that could represent an efficient strategy used by ASFV to evade the innate immune response |
|
| dc.description |
This work was supported by grants from Ministerio de Educación y Ciencia
(BFU2004-00298/BMC), the Wellcome Trust (075813/C/04/z), and by an institutional
grant from the Fundación Ramón Areces. C.H. was a fellow from Fundación
Ramón Areces. |
|
| dc.description |
Peer reviewed |
|
| dc.format |
3436629 bytes |
|
| dc.format |
application/pdf |
|
| dc.language |
eng |
|
| dc.publisher |
American Association of Immunologists |
|
| dc.rights |
openAccess |
|
| dc.subject |
ASFV |
|
| dc.subject |
A238L protein |
|
| dc.title |
The Viral Protein A238L Inhibits TNF-α Expression through a CBP/p300 Transcriptional Coactivators Pathway |
|
| dc.type |
Artículo |
|