Suppression of steady-state, but not stimulus-induced NF-κB activity inhibits alphavirus-induced apoptosis

Recent studies have established cell type-specific, proapoptotic, or antiapoptotic functions for the transcription factor NF-κB. In each of these studies, inhibitors of NF-κB activity have been present before the apoptotic stimulus, and so the role of stimulus-induced NF-κB activation in enhancing or inhibiting survival could not be directly assessed. Sindbis virus, an alphavirus, induces NF-κB activation and apoptosis in cultured cell lines. To address whether Sindbis virus-induced NF-κB activation is required for apoptosis, we used a chimeric Sindbis virus that expresses a superrepressor of NF-κB activity. Complete suppression of virus-induced NF-κB activity neither prevents nor potentiates Sindbis virus-induced apoptosis. In contrast, inhibition of NF-κB activity before infection inhibits Sindbis virus-induced apoptosis. Our results demonstrate that suppression of steady- state, but not stimulus-induced NF-κB activity, regulates expression of gene products required for Sindbis virus-induced death. Furthermore, we show that in the same cell line, NF-κB can be proapoptotic or antiapoptotic depending on the death stimulus. We propose that the role of NF-κB in regulating apoptosis is determined by the death stimulus and by the timing of modulating NF-κB activity relative to the death stimulus.