DEFECTIVE HERPES-SIMPLEX VIRUS VECTORS EXPRESSING THE RAT-BRAIN STRESS-INDUCIBLE HEAT-SHOCK PROTEIN-72 PROTECT CULTURED NEURONS FROM SEVEREHEAT-SHOCK

Recently, preinduction of the heat shock response has been shown to pr otect CNS neurons undergoing various stressful insults, e.g., heat, is chemia, or exposure to excitotoxins, However, it is not known which of the proteins induced by the heat shock response mediate the protectiv e effects. Previous correlative evidence points to a role for the high ly stress-induced 72-kDa heat shock protein (hsp72). However, it is no t known whether hsp72 expression alone can protect against a range of acute neuronal insults. We constructed a herpes simplex virus-1 vector carrying the rat brain stress-inducible hsp72 gene and the Escherichi a coli lacZ (marker) gene, Infection with the vector caused hippocampa l neurons to coexpress hsp72 and beta-galactosidase. Infection with a control vector led to marker gene expression only. Overexpression of h sp72 protected cultured hippocampal neurons against a heat shock but n ot against the metabolic toxin 3-nitropropionic acid or the excitotoxi n glutamate. This is the first published report of protection followin g heat shock protein transfection in CNS neurons.