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Calcium and the ERK1/2-CREB pathway regulate HSV-1 gene expression in rat primary sensory neurons.
Sensory neurons express immediate-early (IE) genes after stimulation by the herpes simplex virus (HSV-1). To understand the calcium-calcineurin/NFAT pathway and mitogen-activated protein kinase (MAPK) pathways in HSV-1 gene expression, we examined the signals responsible for the induction of the expression of IE genes in sensory neurons. C5a, an activator of the protein kinase C (PKC) and a major component of the complement cascade, increased the expression of ICP0 and ICP4 genes in sensory neurons, and this was blocked by a MAPK inhibitor, ERK1/2. Furthermore, the CREB phosphorylation, a consequence of ERK1/2 activation, also increased. siRNA transfection analysis suggested that the increase of CREB phosphorylation is mediated by ERK1/2-CREB pathway. These results suggest that the ERK1/2-CREB pathway, in addition to the calcineurin/NFAT pathway, is involved in the induction of HSV-1 IE genes and the activation of IE genes in sensory neurons.: The death to the collective
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