| Entry kinetics and cell-cell transmission of surface-bound retroviral vector particles. | |
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MedLine Citation:
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PMID: 20440757 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Transduction with recombinant HIV-1 derived lentivirus vectors is a multi-step process initiated by surface attachment and subsequent receptor-directed uptake into the target cell. We previously reported the retention of vesicular stomatitis virus G protein pseudotyped particles on murine progenitor cells and their delayed cell-cell transfer. METHODS: To examine the underlying mechanism in more detail, we used a combination of approaches focused on investigating the role of receptor-independent factors in modulating attachment. RESULTS: The investigation of synchronized transduction reveals cell-type specific rates of vector particle clearance with substantial delays during particle entry into murine hematopoietic progenitor cells. The observed uptake kinetics from the surface of the 1 degrees cell correlate inversely with the magnitude of transfer to 2 degrees targets, corresponding with our initial observation of preferential cell-cell transfer in the context of brief vector exposures. We further demonstrate that vector particle entry into cells is associated with the cell-type specific abundance of extracellular matrix fibronectin. Residual particle-extracellular fibronectin matrix binding and 2 degrees transfer can be competitively disrupted by heparin exposure without affecting murine progenitor homing and repopulation. CONCLUSIONS: Although cellular attachment factors, including fibronectin, aid gene transfer by colocalizing particles to cells and disfavoring early dissociation from targets, they also appear to stabilize particles on the cell surface. The present study highlights the inadvertent consequences for cell entry and cell-cell transfer. |
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Authors:
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Lee S O'Neill; Amy M Skinner; Josha A Woodward; Peter Kurre |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The journal of gene medicine Volume: 12 ISSN: 1521-2254 ISO Abbreviation: J Gene Med Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-05-04 Completed Date: 2011-03-10 Revised Date: 2011-07-28 |
Medline Journal Info:
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Nlm Unique ID: 9815764 Medline TA: J Gene Med Country: England |
Other Details:
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Languages: eng Pagination: 463-76 Citation Subset: IM |
Copyright Information:
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Copyright (c) 2010 John Wiley & Sons, Ltd. |
Affiliation:
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Department of Pediatrics, Papé Family Pediatric Research Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Bone Marrow Cells / cytology, drug effects, virology Cell Communication* / drug effects Cell Line Cell Lineage / drug effects Cell Membrane / drug effects, metabolism, virology* Extracellular Matrix / drug effects, metabolism Fibronectins / metabolism Genetic Vectors / metabolism* Green Fluorescent Proteins / metabolism Heparin / pharmacology Humans Kinetics Mice Peptide Hydrolases / metabolism Proviruses / drug effects, metabolism Retroviridae / drug effects, metabolism* Time Factors Transduction, Genetic Virion / drug effects, metabolism* Virus Integration / drug effects Virus Internalization* / drug effects Whole-Body Irradiation |
| Grant Support | |
ID/Acronym/Agency:
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HL77231/HL/NHLBI NIH HHS; HL90765/HL/NHLBI NIH HHS; K08 HL077231-05/HL/NHLBI NIH HHS; R01 HL090765-02/HL/NHLBI NIH HHS; R01 HL090765-04/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Fibronectins; 147336-22-9/Green Fluorescent Proteins; 9005-49-6/Heparin; EC 3.4.-/Peptide Hydrolases |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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