Abstract
1059. The Lymphocytic Choriomeningitis Virus Envelope Glycoprotein Targets Lentivirus to Neural Progenitors in the Murine Brain
Molecular therapy, Vol.9(S1), pp.S406-S406
05/01/2004
DOI: 10.1016/j.ymthe.2004.06.1004
Abstract
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) strain WE54 envelope glycoprotein was injected unilaterally into the mouse brain striatum to determine neural cell-type transduction. At 3 weeks and 7 weeks, beta-gal-expressing cells were found in the striatum, in the subventricular zone of the lateral ventricle, along the rostral migratory stream, and in the olfactory bulb on the injected side. Immunofluorescent staining and confocal microscopy showed that transgene expression in the striatum and the subventricular zone co-localized predominantly with glial fibrillary acidic protein (GFAP), an astrocyte cell marker. Beta-gal positive cells in the olfactory bulb were dispersed throughout the parenchyma, and cell morphology and staining with a neuronal cell marker demonstrated that these cells were neurons. Within the rostral migratory stream, co-localization of beta-gal with class III beta-tubulin identified these cells as migratory neuroblasts. This pattern of transgene expression was suggestive of neural progenitor cell transduction and we hypothesized that GFAP-expressing neural progenitors within the subventricular zone (type B astrocytes) were transduced. To test this, an LCMV-pseudotyped FIV vector with the GFAP promoter driving expression of cre recombinase was injected into "loxP stop loxP beta-gal" transgenic reporter mice. Beta-gal expression in these mice is dependent on cre recombinase-mediated DNA recombination. Seven weeks after unilateral injection into the striatum, beta-gal positive neurons were detected in the ipsilateral olfactory bulb, and beta-gal positive neuroblasts were detected in the rostral migratory stream on the ipsilateral side. Beta-gal expression indicated that these cells derived from a transduced GFAP-expressing precursor, most likely the type B astrocyte. Thus, LCMV(WE54)-pseudotyped FIV provides a novel vector for transducing neural progenitors in vivo.
Details
- Title: Subtitle
- 1059. The Lymphocytic Choriomeningitis Virus Envelope Glycoprotein Targets Lentivirus to Neural Progenitors in the Murine Brain
- Creators
- Colleen SteinInes MartinsBeverly Davidson
- Resource Type
- Abstract
- Publication Details
- Molecular therapy, Vol.9(S1), pp.S406-S406
- Publisher
- Elsevier Limited
- DOI
- 10.1016/j.ymthe.2004.06.1004
- ISSN
- 1525-0016
- eISSN
- 1525-0024
- Language
- English
- Date published
- 05/01/2004
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984618620802771
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