Protection of neuronal cells from apoptosis by hsp27 delivered with a herpes simplex virus-based vector

Overexpression of the gene encoding the 70-kDa heat shock protein (hsp70) has previously been shown to protect neuronal cells against subsequent thermal or ischemic stress. It has no protective effect, however, against stimuli that induce apoptosis, although a mild heat shock (sufficient to induce hsp synthesis) does have a protective effect against apoptosis. We have prepared disabled herpes simplex virus-based vectors that are able to produce high level expression of individual hsps in infected neuronal cells without damaging effects. We have used these vectors to show that hsp27 and hsp56 (which have never previously been overexpressed in neuronal cells) as well as hsp70 can protect dorsal root ganglion neurons from thermal or ischemic stress. In contrast, only hsp27 can protect dorsal root ganglion neurons from apoptosis induced by nerve growth factor withdrawal, and hsp27 also protects the ND7 neuronal cell line from retinoic acid-induced apoptosis. However, hsp70 showed no protective effect against apoptosis in contrast to its anti-apoptotic effect in non-neuronal cell types. These results thus identify hsp27 as a novel neuroprotective factor and show that it can mediate this effect when delivered via a high efficiency viral vector.