PMID:17881445

Citation	de Los Santos, T, Diaz-San Segundo, F and Grubman, MJ (2007) Degradation of nuclear factor kappa B during foot-and-mouth disease virus infection. J. Virol. 81:12803-15
Abstract	We have previously shown that the leader proteinase (L(pro)) of foot-and-mouth disease virus (FMDV) interferes with the innate immune response by blocking the translation of interferon (IFN) protein and by reducing the immediate-early induction of beta IFN mRNA and IFN-stimulated genes. Here, we report that L(pro) regulates the activity of nuclear factor kappaB (NF-kappaB). Analysis of NF-kappaB-dependent reporter gene expression in BHK-21 cells demonstrated that infection with wild-type (WT) virus has an inhibitory effect compared to infection with a genetically engineered mutant lacking the leader coding region. The expression of endogenous NF-kappaB-dependent genes tumor necrosis factor alpha and RANTES is also reduced in WT virus-infected primary porcine cells. This inhibitory effect is neither the result of a decrease in the level of the mRNA of p65/RelA, a subunit of NF-kappaB, nor a block on the nuclear translocation of p65/RelA, but instead appears to be a consequence of the degradation of accumulated p65/RelA. Viral L(pro) is localized to the nucleus of infected cells, and there is a correlation between the translocation of L(pro) and the decrease in the amount of nuclear p65/RelA. By using a recombinant cardiovirus expressing L(pro), we demonstrate that the disappearance of p65/RelA takes place in the absence of any other FMDV product. The observation that L(pro) disrupts the integrity of NF-kappaB suggests a global mechanism by which FMDV antagonizes the cellular innate immune and inflammatory responses to viral infection.
Links	PubMed PMC2169123 Online version:10.1128/JVI.01467-07
Keywords	Animals; Artificial Gene Fusion; Cell Line; Cell Nucleus/chemistry; Cells, Cultured; Chemokine CCL5/biosynthesis; Cricetinae; Endopeptidases/metabolism; Foot-and-Mouth Disease Virus/immunology; Gene Deletion; Gene Expression; Genes, Reporter; Luciferases/biosynthesis; Swine; Transcription Factor RelA/antagonists & inhibitors; Transcription Factor RelA/metabolism; Tumor Necrosis Factor-alpha/biosynthesis
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
FMDVO:POLG	involved_in	GO:0039644: suppression by virus of host NF-kappaB transcription factor activity	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
FMDVO:POLG	part_of	GO:0030430: host cell cytoplasm	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
FMDVO:POLG	part_of	GO:0042025: host cell nucleus	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
FMDVO:POLG	involved_in	GO:0039502: suppression by virus of host type I interferon-mediated signaling pathway	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete

References

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