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http://dspace.mediu.edu.my:8181/xmlui/handle/10261/4921| Title: | The Viral Protein A238L Inhibits TNF-α Expression through a CBP/p300 Transcriptional Coactivators Pathway |
| Authors: | Ministerio de Educación y Ciencia (España) Wellcome Trust Fundación Ramón Areces |
| Keywords: | ASFV A238L protein |
| Publisher: | American Association of Immunologists |
| Description: | Article available at http://www.jimmunol.org/cgi/content/abstract/176/1/451 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 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. Peer reviewed |
| URI: | http://dspace.mediu.edu.my:8181/xmlui/handle/10261/4921 |
| Other Identifiers: | The Journal of Immunology, 2006, 176: 451-462 0022-1767 (Print) 1550-6606 (Online) http://hdl.handle.net/10261/4921 |
| Appears in Collections: | Digital Csic |
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