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

Colleen S Stein; Inês Martins; Beverly L Davidson

doi:10.1016/j.ymthe.2004.11.008

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

Journal article

Open access

Peer reviewed

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

Colleen S Stein, Inês Martins and Beverly L Davidson

Molecular therapy, Vol.11(3), pp.382-389

03/2005

DOI: 10.1016/j.ymthe.2004.11.008

PMID: 15727934

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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) 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.

Animals

Astrocytes - metabolism

Astrocytes - virology

Brain - metabolism

Brain - virology

Bromodeoxyuridine - metabolism

Corpus Striatum - metabolism

Corpus Striatum - virology

Genetic Vectors

Glycoproteins - genetics

Glycoproteins - metabolism

Lentivirus - genetics

Lentivirus - metabolism

Lymphocytic choriomeningitis virus - metabolism

Mice

Transgenes

Viral Envelope Proteins - genetics

Viral Envelope Proteins - metabolism

Details

Title: Subtitle: The lymphocytic choriomeningitis virus envelope glycoprotein targets lentiviral gene transfer vector to neural progenitors in the murine brain
Creators: Colleen S Stein - University of Iowa
Inês Martins - University of Iowa
Beverly L Davidson - University of Iowa
Resource Type: Journal article
Publication Details: Molecular therapy, Vol.11(3), pp.382-389
DOI: 10.1016/j.ymthe.2004.11.008
PMID: 15727934
ISSN: 1525-0016
eISSN: 1525-0024
Grant note: DK54759 / NIDDK NIH HHS NS34568 / NINDS NIH HHS
Language: English
Date published: 03/2005
Academic Unit: Internal Medicine
Record Identifier: 9984618647402771

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