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J. Virol. doi:10.1128/JVI.00806-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

AN AKT1-DEPENDENT ACTIVATION OF NF-B BY THE L PROTEIN OF PARAINFLUENZA VIRUS 5 (PIV5)

Intercollege Graduate Program in Cell and Developmental Biology, Department of Veterinary and Biomedical Sciences, Center of Molecular Immunology and Infectious Disease, Pennsylvania State University, University Park, PA 16802

^* To whom correspondence should be addressed. Email: bxh40{at}psu.edu.

	Abstract

Innate immunity plays a critical role in the control of viral infections. The induction of innate immune responses requires activation of transcription factors. In particular, NF-B plays an essential role in activating the expression of cytokines involved in innate immunity such as interferon - (IFN-) and interleukin - 6 (IL-6). However, the mechanisms by which viruses activate NF-B are poorly defined. Infection by parainfluenza virus 5 (PIV5), a prototypical member of the Paramyxoviridae family of Mononegavirales, has been shown to activate the expression of IFN- and IL-6. To examine how PIV5 induces this expression, we have examined the activation of NF-B by PIV5 proteins. We have found that expression of PIV5 L protein alone is sufficient to activate NF-B. The L protein of PIV5, the catalytic component of the viral RNA-dependent RNA polymerase, contains six domains that are conserved among all negative-stranded non-segmented RNA viruses. We have mapped the region that activates NF-B to the second domain, which is thought to be involved in RNA synthesis. The activation of NF-B by L requires AKT1, a serine/threonine kinase, since AKT1 siRNA, AKT inhibitor as well as a dominant negative mutant of AKT1 blocks this activation. Furthermore, we have found that L interacts with AKT1 and enhances its phosphorylation. We speculate that L may encode AKT1 kinase activity.