AKT1-dependent activation of NF-kappaB by the L protein of parainfluenza virus 5.
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-kappaB plays an essential role in activating the expression of cytokines involved in innate immunity such as beta interferon (IFN-beta) and interleukin-6 (IL-6). However, the mechanisms by which viruses activate NF-kappaB 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-beta and IL-6. To examine how PIV5 induces this expression, we have examined the activation of NF-kappaB by PIV5 proteins. We have found that expression of PIV5 L protein alone is sufficient to activate NF-kappaB. 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-kappaB to the second domain, which is thought to be involved in RNA synthesis. The activation of NF-kappaB 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.
Luthra
Priya
P
Department of Veterinary and Biomedical Sciences, Intercollege Graduate Program in Cell and Developmental Biology, Pennsylvania State University, University Park, Pennsylvania 16802, USA.
Sun
Dengyun
D
Wolfgang
Matthew
M
He
Biao
B
D000818:Animals; D002460:Cell Line; D051379:Mice; D016328:NF-kappa B / Q000276:immunology* / Q000378:metabolism*; D010252:Paramyxoviridae / Q000276:immunology* / Q000502:physiology*; D025941:Protein Interaction Mapping; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
C431770:L protein, paramyxoviridae; D016328:NF-kappa B; D014764:Viral Proteins; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt