Identification of PDGFR as a receptor for AAV-5 transduction.
Understanding the process of vector transduction has important implications for the application and optimal use of a vector system for human gene therapy. Recent studies with vectors based on adeno-associated virus type 5 (AAV-5) have shown utility of this vector system in the lung, central nervous system, muscle and eye. To understand the natural tropism of this virus and to identify proteins necessary for AAV-5 transduction, we characterized 43 cell lines as permissive or nonpermissive for AAV-5 transduction and compared the gene expression profiles derived from cDNA microarray analyses of those cell lines. A statistically significant correlation was observed between expression of the platelet-derived growth factor receptor (PDGFR-alpha-polypeptide) and AAV-5 transduction. Subsequent experiments confirmed the role of PDGFR-alpha and PDGFR-beta as receptors for AAV-5. The tropism of AAV-5 in vivo also correlated with the expression pattern of PDGFR-alpha.
D000818:Animals; D002460:Cell Line; D000229:Dependovirus / Q000235:genetics* / Q000378:metabolism*; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism*; D013223:Statistics as Topic; D014161:Transduction, Genetic
D020033:Protein Isoforms; D066246:ErbB Receptors; D017479:Receptors, Platelet-Derived Growth Factor