1. ¹Centre for Infectious Diseases, Royal School of Veterinary Studies, College of Medicine and Veterinary Medicine, University of Edinburgh, Summerhall, Edinburgh EH9 1QH, Scotland, UK
2. ²Division of Veterinary Clinical Studies, Royal School of Veterinary Studies, College of Medicine and Veterinary Medicine, University of Edinburgh, Summerhall, Edinburgh EH9 1QH, Scotland, UK

Correspondence: John K. Fazakerley, Fax: +44 131 650 6511. E-mail: John.Fazakerley@ed.ac.uk

Received 21 June 2005; Revised 21 October 2005; Accepted 25 October 2005.

Abstract

The Semliki Forest virus (SFV) 1 vector system is highly efficient at gene transduction in a broad range of host cells, including neurons. To determine the potential of SFV1-based vectors to mediate gene expression in substantia nigra neurons, we inoculated d1EGFP-expressing SFV virus-like particles stereotaxically into the mouse brain. This system selectively and extensively mediated gene expression in dopaminergic neurons of the substantia nigra. Continual reporter gene expression was evident in neuronal cell bodies for up to 3 weeks postinoculation and d1EGFP-positive neuronal processes were apparent for 12 weeks. There was no evidence of an apoptotic response to infection, but with time cell degeneration and an axonopathy, indicative of neuronal loss, were increasingly apparent. This system has potential for experimental studies requiring efficient transient gene transduction of mouse CNS neurons. The current SFV1 vector system is, however, limited in its potential for CNS gene therapy by neurotoxicity.