The lymphocytic choriomeningitis virus envelope glycoprotein targets lentiviral gene transfer vector to neural progenitors in the murine brain.

Feline immunodeficiency virus (FIV)-based lentiviral vectors can be targeted to restricted cell types by pseudotyping with envelopes from other viruses. An FIV vector expressing bacterial beta-galactosidase (beta-gal) and pseudotyped with lymphocytic choriomeningitis virus (LCMV) envelope glycoprotein was injected into postnatal mouse brain striatum to determine neural cell-type transduction. After 3 or 7.5 weeks, the beta-gal-expressing cells included astrocytes in the striatum and in the subventricular zone (SVZ), neuroblasts along the rostral migratory stream, and neurons in the olfactory bulb. This pattern was suggestive of transduction of neural stem cells/progenitors that reside in the SVZ and continually generate olfactory bulb neurons. To test for transduction of SVZ type B astrocyte/stem cells, LCMV-pseudotyped FIV encoding Cre recombinase driven by an astrocyte-specific promoter was injected into the striatum of ROSA26 Cre reporter mice. beta-Gal expression in these mice depends on Cre recombinase-mediated DNA recombination. beta-Gal-expressing neuroblasts and neurons were detected in the rostral migratory stream and olfactory bulb, respectively, indicating that these cells derived from an astrocytic-type stem cell. Thus, LCMV (WE54)-pseudotyped FIV provides a novel vector for transducing neural stem cells/progenitors in vivo and may prove valuable as a gene transfer vector for therapy of neurodegenerative diseases.