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Title

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

AuthorsGranja, Aitor G. ; Sabina, Prado ; Salas, María Luisa; Fresno, Manuel ; Revilla Novella, Yolanda
KeywordsNitric-oxide synthase
A238L virus protein
Issue Date2006
PublisherAmerican Society for Microbiology
CitationJournal of Virology, p. 10487-10496, Vol. 80, No. 21
AbstractUncontrolled 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-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-) 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--induced iNOS promoter activity. Following stimulation with LPS-IFN-, p65 and p300 interaction was abolished in Raw-A238L cells. Expression of A238L also inhibited p65/relA and p300 binding to the distal NF-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
Publisher version (URL)http://dx.doi.org/10.1128/JVI.00862-06
URIhttp://hdl.handle.net/10261/8027
DOI10.1128/JVI.00862-06
ISSN0022-538X
E-ISSN1098-5514
Appears in Collections:(CBM) Artículos
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