|De Los Santos, Teresa|
|Diaz San-Segundo, Fayna - ORISE, USDA, ARS, PIADC|
Submitted to: American Society for Virology Meeting
Publication Type: Abstract Only
Publication Acceptance Date: April 12, 2007
Publication Date: July 14, 2007
Citation: De Los Santos, T., Diaz San-Segundo, F., Grubman, M.J., 2007, Degradation of Nuclear Factor Kappa B During Foot-and-Mouth Disease Virus Infection. American Society for Virology Meeting. W1-3, p.71 Technical Abstract: We have previously shown that wild-type foot-and-mouth disease virus (FMDV) interferes with the immune response by blocking the expression of interferon (IFN) protein and by reducing the immediate-early induction of IFN beta mRNA and IFN stimulated genes. This effect is directly associated with the presence of the viral leader proteinase (L pro). Here we show that L pro is involved in reducing the activity of the transcription factor NF kappa B. Analysis of NF kappa B dependent reporter gene expression in BHK-21 cells indicated that whereas wild-type FMDV blocks induction of NF kappa B transcriptional activity, a genetically engineered FMDV mutant lacking the L pro coding region (leaderless virus) does not. In addition, wild-type virus inhibited the NF kappa B dependent reporter activity induced by transfected synthetic dsRNA (poly[IC]). Consistent with these results, infection of porcine cells with leaderless virus induced higher levels of mRNA for the NF kappa B inducible cytokine TNF alpah and the chemokine RANTES when compared to infection with wild-type virus. Apparently wild-type FMDV does not affect the activation of the p65/RelA subunit of NF kappa B, reflected by the translocation of this protein to the nucleus, but rather induces the degradation of cytoplasmic and accumulated nuclear protein. Disappearance of p65 correlates with the expression and translocation of L pro to the nucleus. No general effect on protein sub-cellular distribution or degradation was observed with a nucleus-targeted green fluorescent protein. Apoptosis was ruled out as the cause of NF kappa B degradation during FMDV infection. The observation that L pro disrupts the integrity of NF kappa B suggests a new mechanism by which FMDV antagonizes the cellular immune and inflammatory response to viral infection.