| The host range of gammaretroviruses and gammaretroviral vectors includes post-mitotic neural cells. | |
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MedLine Citation:
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PMID: 21464894 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Gammaretroviruses and gammaretroviral vectors, in contrast to lentiviruses and lentiviral vectors, are reported to be restricted in their ability to infect growth-arrested cells. The block to this restriction has never been clearly defined. The original assessment of the inability of gammaretroviruses and gammaretroviral vectors to infect growth-arrested cells was carried out using established cell lines that had been growth-arrested by chemical means, and has been generalized to neurons, which are post-mitotic. We re-examined the capability of gammaretroviruses and their derived vectors to efficiently infect terminally differentiated neuroendocrine cells and primary cortical neurons, a target of both experimental and therapeutic interest. METHODOLOGY/PRINCIPAL FINDINGS: Using GFP expression as a marker for infection, we determined that both growth-arrested (NGF-differentiated) rat pheochromocytoma cells (PC12 cells) and primary rat cortical neurons could be efficiently transduced, and maintained long-term protein expression, after exposure to murine leukemia virus (MLV) and MLV-based retroviral vectors. Terminally differentiated PC12 cells transduced with a gammaretroviral vector encoding the anti-apoptotic protein Bcl-xL were protected from cell death induced by withdrawal of nerve growth factor (NGF), demonstrating gammaretroviral vector-mediated delivery and expression of genes at levels sufficient for therapeutic effect in non-dividing cells. Post-mitotic rat cortical neurons were also shown to be susceptible to transduction by murine replication-competent gammaretroviruses and gammaretroviral vectors. CONCLUSIONS/SIGNIFICANCE: These findings suggest that the host range of gammaretroviruses includes post-mitotic and other growth-arrested cells in mammals, and have implications for re-direction of gammaretroviral gene therapy to neurological disease. |
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Authors:
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Xiu-Huai Liu; Wenqin Xu; Jill Russ; Lee E Eiden; Maribeth V Eiden |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Intramural Date: 2011-03-28 |
Journal Detail:
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Title: PloS one Volume: 6 ISSN: 1932-6203 ISO Abbreviation: PLoS ONE Publication Date: 2011 |
Date Detail:
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Created Date: 2011-04-05 Completed Date: 2011-07-18 Revised Date: 2011-07-28 |
Medline Journal Info:
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Nlm Unique ID: 101285081 Medline TA: PLoS One Country: United States |
Other Details:
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Languages: eng Pagination: e18072 Citation Subset: IM |
Affiliation:
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Section on Molecular Neuroscience, Laboratory of Cellular and Molecular Regulation, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, United States of America. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Death / drug effects Cell Differentiation / drug effects Cell Proliferation / drug effects Cerebral Cortex / cytology DNA / metabolism G2 Phase / drug effects Gammaretrovirus / drug effects, genetics* Genetic Vectors / genetics* Green Fluorescent Proteins / metabolism Host Specificity / drug effects, physiology* Lentivirus / drug effects, genetics Mitosis* / drug effects Nerve Growth Factor / pharmacology Neurons / cytology*, drug effects, virology* PC12 Cells Rats S Phase / drug effects Serum Transduction, Genetic bcl-X Protein / metabolism |
| Chemical | |
Reg. No./Substance:
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0/bcl-X Protein; 147336-22-9/Green Fluorescent Proteins; 9007-49-2/DNA; 9061-61-4/Nerve Growth Factor |
| Comments/Corrections | |
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