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Journal of Virology, December 2007, p. 12803-12815, Vol. 81, No. 23
0022-538X/07/$08.00+0     doi:10.1128/JVI.01467-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Degradation of Nuclear Factor Kappa B during Foot-and-Mouth Disease Virus Infection{triangledown}

Teresa de los Santos, Fayna Diaz-San Segundo, and Marvin J. Grubman*

Plum Island Animal Disease Center, Agricultural Research Service, U.S. Department of Agriculture, Greenport, New York 11944

Received 5 July 2007/ Accepted 4 September 2007

We have previously shown that the leader proteinase (Lpro) 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 Lpro regulates the activity of nuclear factor {kappa}B (NF-{kappa}B). Analysis of NF-{kappa}B-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-{kappa}B-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-{kappa}B, 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 Lpro is localized to the nucleus of infected cells, and there is a correlation between the translocation of Lpro and the decrease in the amount of nuclear p65/RelA. By using a recombinant cardiovirus expressing Lpro, we demonstrate that the disappearance of p65/RelA takes place in the absence of any other FMDV product. The observation that Lpro disrupts the integrity of NF-{kappa}B suggests a global mechanism by which FMDV antagonizes the cellular innate immune and inflammatory responses to viral infection.

* Corresponding author. Mailing address: Plum Island Animal Disease Center, ARS, NAA, USDA, P.O. Box 848, Greenport, NY 11944. Phone: (631) 323-3329. Fax: (631) 323-3006. E-mail: marvin.grubman{at}ars.usda.gov

{triangledown} Published ahead of print on 19 September 2007.

Journal of Virology, December 2007, p. 12803-12815, Vol. 81, No. 23
0022-538X/07/$08.00+0     doi:10.1128/JVI.01467-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Morrison, J. M., Racaniello, V. R. (2009). Proteinase 2Apro Is Essential for Enterovirus Replication in Type I Interferon-Treated Cells. J. Virol. 83: 4412-4422 [Abstract] [Full Text]  
  • de los Santos, T., Diaz-San Segundo, F., Zhu, J., Koster, M., Dias, C. C. A., Grubman, M. J. (2009). A Conserved Domain in the Leader Proteinase of Foot-and-Mouth Disease Virus Is Required for Proper Subcellular Localization and Function. J. Virol. 83: 1800-1810 [Abstract] [Full Text]  


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