This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Granja, A. G.
Right arrow Articles by Revilla, Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Granja, A. G.
Right arrow Articles by Revilla, Y.

 Previous Article  |  Next Article 

Journal of Virology, November 2006, p. 10487-10496, Vol. 80, No. 21
0022-538X/06/$08.00+0     doi:10.1128/JVI.00862-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Regulation of Inducible Nitric Oxide Synthase Expression by Viral A238L-Mediated Inhibition of p65/RelA Acetylation and p300 Transactivation

Aitor G. Granja, Prado Sabina, María L. Salas, Manuel Fresno, and Yolanda Revilla*

Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid, 28049 Madrid, Spain

Received 27 April 2006/ Accepted 31 July 2006

Uncontrolled generation of nitric oxide (NO) by inducible nitric-oxide synthase (iNOS) can cause damage to host cells and inflammation, two undesirable events for virus spreading. African swine fever virus (ASFV) infection regulates iNOS-induced gene expression through the synthesis of the A238L virus protein. We here explored the role of A238L, an NF-{kappa}B and NFAT inhibitor, in the regulation of iNOS transcription in macrophages. NO production and iNOS mRNA and protein levels as well as iNOS promoter activity after lipopolysaccharide (LPS)-gamma interferon (IFN-{gamma}) treatment were down-regulated both during ASFV infection and in Raw 264.7 cells stably expressing the viral protein. Overexpression of p300, but not of a histone acetyltransferase (HAT) defective mutant, reverted the A238L-mediated inhibition of both basal and LPS-IFN-{gamma}-induced iNOS promoter activity. Following stimulation with LPS-IFN-{gamma}, p65 and p300 interaction was abolished in Raw-A238L cells. Expression of A238L also inhibited p65/relA and p300 binding to the distal NF-{kappa}B sequence of the iNOS promoter together with p65 acetylation. Finally, A238L abrogated p300 transactivation mediated by a GAL4-p300 construction. These results provide evidence for an unique viral mechanism involved in transcriptional regulation of iNOS gene expression.

* Corresponding author. Mailing address: Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid, Madrid 28049, Spain. Phone: 34914978486. Fax: 34914974799. E-mail: yrevilla{at}cbm.uam.es.

Journal of Virology, November 2006, p. 10487-10496, Vol. 80, No. 21
0022-538X/06/$08.00+0     doi:10.1128/JVI.00862-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Granja, A. G., Sanchez, E. G., Sabina, P., Fresno, M., Revilla, Y. (2009). African Swine Fever Virus Blocks the Host Cell Antiviral Inflammatory Response through a Direct Inhibition of PKC-{theta}-Mediated p300 Transactivation. J. Virol. 83: 969-980 [Abstract] [Full Text]  
  • Granja, A. G., Perkins, N. D., Revilla, Y. (2008). A238L Inhibits NF-ATc2, NF-{kappa}B, and c-Jun Activation through a Novel Mechanism Involving Protein Kinase C-{theta}-Mediated Up-Regulation of the Amino-Terminal Transactivation Domain of p300. J. Immunol. 180: 2429-2442 [Abstract] [Full Text]  
  • Stoltz, M., Ahlm, C., Lundkvist, A., Klingstrom, J. (2007). Lambda Interferon (IFN-{lambda}) in Serum Is Decreased in Hantavirus-Infected Patients, and In Vitro-Established Infection Is Insensitive to Treatment with All IFNs and Inhibits IFN-{gamma}-Induced Nitric Oxide Production. J. Virol. 81: 8685-8691 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»