Adeno-associated virus type 2 vectors: transduction and long-term expression in cerebellar Purkinje cells in vivo is mediated by the fibroblast growth factor receptor 1 : bFGFR-1 mediates AAV2 transduction of Purkinje cells

Arch Virol. 2008;153(11):2107-10. doi: 10.1007/s00705-008-0222-7. Epub 2008 Oct 21.

Abstract

The receptor for adeno-associated virus serotype 2 (AAV2) in Purkinje cells has not been identified, but based on work carried out in non-neuronal cell lines, heparan sulfate proteoglycan is thought to act as a primary receptor, with basic fibroblast growth factor receptor-1 being reported as a co-receptor. In this study, using antibody interference and protein competition strategies, we show specific reduction in Purkinje cell transduction by AAV2 vector in the presence of these inhibitors. We also demonstrate AAV2-mediated transgene expression in Purkinje cells in vivo that extends out to one year post-injection. These results provide new information on fibroblast growth factor receptor-1 involvement in AAV2-mediated transduction of Purkinje cells and have important implications for AAV-mediated treatment of various cerebellar disorders.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Brain / metabolism
  • Brain / virology
  • Dependovirus / genetics*
  • Dependovirus / metabolism
  • Female
  • Gene Expression*
  • Gene Transfer Techniques*
  • Genetic Vectors / genetics*
  • Mice
  • Purkinje Cells / metabolism*
  • Purkinje Cells / virology
  • Receptor, Fibroblast Growth Factor, Type 1 / genetics
  • Receptor, Fibroblast Growth Factor, Type 1 / metabolism*
  • Transduction, Genetic*

Substances

  • Receptor, Fibroblast Growth Factor, Type 1