1. ¹Department of Molecular Biomedical Sciences, North Carolina State University, Raleigh, NC, USA
2. ²Department of Medicine, University of North Carolina, Chapel Hill, NC, USA
3. ³Gill Center for Biomolecular Science, Indiana University, Bloomington, IN, USA
4. ⁴Neuroscience Research Center, University of North Carolina, Chapel Hill, NC, USA

Correspondence: Dr HT Ghashghaei, Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA. E-mail: Troy_Ghashghaei@ncsu.edu

⁵These authors contributed equally.

Received 21 January 2009; Revised 17 March 2009; Accepted 22 March 2009; Published online 28 May 2009.

Abstract

Ongoing neurogenesis in discrete sectors of the adult central nervous system depends on the mitotic activity of an elusive population of adult stem cells. The existence of adult neural stem cells provides an alternative approach to transplantation of embryonic stem cells in cell-based therapies. Owing to the limited intrinsic fate of adult stem cells and inhibitory nature of the adult brain for neurogenesis, accommodation for circuit replacement in the brain will require genetic and epigenetic manipulation. Here, we show that a replication-incompetent Equine Infectious Anemia Virus (EIAV) is highly suitable for stable and persistent gene transfer to adult neural stem cells. The transduced regions were free of long-lasting neuroimmune responses to EIAV. Transduction in the subventricular zone was specific to the stem cell niche, but spared the progeny of adult neural stem cells that includes transit amplifying progenitors (TAPs) and migrating neuroblasts. With time, EIAV-transduced stem cells passed on the transgene to TAPs and migrating neuroblasts, which ultimately differentiated into neurons in the olfactory bulbs. We show that EIAV is highly suitable for discovery and assessment of mechanisms that regulate proliferation, migration and differentiation in the postnatal brain.