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Journal of Virology, April 2004, p. 3553-3560, Vol. 78, No. 7
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.7.3553-3560.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

The Vaccinia Virus K1L Gene Product Inhibits Host NF-{kappa}B Activation by Preventing I{kappa}B{alpha} Degradation

Joanna L. Shisler* and Xiao-Lu Jin

Department of Microbiology, College of Medicine, University of Illinois, Urbana, Illinois 61801

Received 10 October 2003/ Accepted 14 November 2003

Vaccinia virus wild-type strains such as Ankara and WR synthesize proteins capable of inhibiting the activation of host NF-{kappa}B, a family of transcription factors that regulate the expression of inflammatory genes. In contrast, an infection by the attenuated MVA strain, whose genome lacks many immunoregulatory genes present in the DNA of its Ankara parent, induces NF-{kappa}B activation. Insertion of NF-{kappa}B inhibitory genes into the MVA DNA, then, would alter the MVA phenotype. By this method, a 5.2-kb region of Ankara DNA containing the K1L gene and two other genes that are absent in the MVA genome that was identified as NF-{kappa}B was inhibited in cells infected with the MVA/5.2kb virus. To determine if K1L was responsible, the relevant biological properties of both a recombinant MVA containing a copy of the WR strain's K1L (MVA/K1L) and a WR deletion mutant lacking the K1L gene ({Delta}K1L) were examined. Indeed, unlike its progenitor, the altered MVA halted degradation of the host regulatory protein I{kappa}B{alpha}—a key event in the pathway of transcriptional activation by NF-{kappa}B factors. Moreover, MVA/K1L gained the ability to repress artificially contrived and natural NF-{kappa}B-regulated expression of a transfected luciferase and the cellular tumor necrosis factor gene, respectively. In contrast, although these functions could also be performed by WR, the {Delta}K1L virus lost these abilities. Thus, one apparent molecular function of K1L is to prevent I{kappa}B{alpha} degradation. This impediment to NF-{kappa}B-induced host proinflammatory gene expression, in turn, might enhance virus survival.

* Corresponding author. Mailing address: Department of Microbiology, College of Medicine, University of Illinois, Urbana, IL 61801. Phone: (217) 265-6450. Fax: (217) 244-6697. E-mail: jshisler{at}uiuc.edu.

Journal of Virology, April 2004, p. 3553-3560, Vol. 78, No. 7
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.7.3553-3560.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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