Differentiation of a human neuroblastoma into neuron-like cells increases their susceptibility to transduction by herpesviral vectors.

Gene transfer is a powerful tool for functional gene analysis in human cells. In this respect, there is a need to develop experimental models that involve homogeneous cultures of human neuron-like cells susceptible to gene transduction and that are easy to handle. Here we describe an optimized and reproducible procedure to differentiate human SH-SY5Y neuroblastoma cells into a homogeneous population of neuron-like cells. The fully differentiated cells are postmitotic and resemble primary cultured neurons in terms of their cytoskeletal polarity. Notably, differentiated SH-SY5Y cells are far more susceptible to transduction by herpes simplex virus (HSV-1)-based vectors than proliferating SH-SY5Y cells. This increase in transduction efficiency after neuronal differentiation may be due to the up-regulation of cell surface receptors for herpesvirus entry. In summary, we propose that fully differentiated human neuron-like cells obtained from the SH-SY5Y neuroblastoma may constitute an excellent and versatile experimental tool for gene transfer and functional genomic studies with HSV-1 vectors.