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Journal of Virology, November 2008, p. 10887-10895, Vol. 82, No. 21
0022-538X/08/$08.00+0     doi:10.1128/JVI.00806-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

AKT1-Dependent Activation of NF-{kappa}B by the L Protein of Parainfluenza Virus 5{triangledown}

Priya Luthra,1 Dengyun Sun,1 Matthew Wolfgang,2 and Biao He1,2,3*

Intercollege Graduate Program in Cell and Developmental Biology,1 Department of Veterinary and Biomedical Sciences,2 Center of Molecular Immunology and Infectious Disease, Pennsylvania State University, University Park, Pennsylvania 168023

Received 15 April 2008/ Accepted 8 August 2008

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-{kappa}B plays an essential role in activating the expression of cytokines involved in innate immunity such as beta interferon (IFN-β) and interleukin-6 (IL-6). However, the mechanisms by which viruses activate NF-{kappa}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-β and IL-6. To examine how PIV5 induces this expression, we have examined the activation of NF-{kappa}B by PIV5 proteins. We have found that expression of PIV5 L protein alone is sufficient to activate NF-{kappa}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 nonsegmented RNA viruses. We have mapped the region that activates NF-{kappa}B to the second domain, which is thought to be involved in RNA synthesis. The activation of NF-{kappa}B by L requires AKT1, a serine/threonine kinase, since AKT1 small interfering RNA, an 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.

* Corresponding author. Mailing address: Center of Molecular Immunology and Infectious Disease, Department of Veterinary and Biomedical Sciences, Pennsylvania State University, 115 Henning Bldg., University Park, PA 16802. Phone: (814) 863-8533. Fax: (814) 863-6140. E-mail: bxh40{at}psu.edu

{triangledown} Published ahead of print on 20 August 2008.

Journal of Virology, November 2008, p. 10887-10895, Vol. 82, No. 21
0022-538X/08/$08.00+0     doi:10.1128/JVI.00806-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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