ANALYSIS OF EVENTS LEADING TO NEURONAL DEATH AFTER INFECTION WITH E1-DEFICIENT ADENOVIRAL VECTORS

Although recombinant adenoviral vectors are being widely used to targe t genes to the nervous system, the cellular and genetic effects of rec ombinant adenoviral infection on neurones function have not been well characterized, Using sympathetic neuronal cultures, we analyzed the ef fect of adenoviral infection on viral and neuronal gene expression and on neuronal function and viability. While a delayed cytotoxicity occu rred 5 days after infection, numerous biochemical and genetic perturba tions occurred within the infected cell prior to this time. This study demonstrates that numerous cellular alterations were produced by reco mbinant adenoviral vectors and, therefore, emphasizes the need for an analysis of the effects of these viral vectors on neuronal function in the interpretation of data regarding transgene expression induced by these vectors in neurons. It also suggests that continued improvements made to the viral vectors themselves might decrease this direct cytot oxicity and lead to improved safety and function of recombinant adenov irus in vivo.