AKT1-Dependent Activation of NF-κB by the L Protein of Parainfluenza Virus 5
Open Access
- 1 November 2008
- journal article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 82 (21), 10887-10895
- https://doi.org/10.1128/jvi.00806-08
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-κB 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-κB are poorly defined. Infection by parainfluenza virus 5 (PIV5), a prototypical member of theParamyxoviridaefamily ofMononegavirales, 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-κB by PIV5 proteins. We have found that expression of PIV5 L protein alone is sufficient to activate NF-κB. 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-κB to the second domain, which is thought to be involved in RNA synthesis. The activation of NF-κB 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.Keywords
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