An HSV-1 vector expressing tyrosine hydroxylase causes production and release of L-DOPA from cultured rat striatal cells

Alfred I. Geller, Matthew J. During, Young J. Oh, Andrew Freese, Karen O'Malley

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41 Scopus citations

Abstract

In this report we demonstrate that a defective herpes simplex virus type one (HSV-1) vector can express enzymatically active tyrosine hydroxylase in cultured striatal cells that are thereby converted into L-DOPA-producing cells. A human tyrosine hydroxylase cDNA (form II) was inserted into an HSV- 1 vector (pHSVth) and packaged into virus particles using an HSV-1 strain 17 mutant in the immediate early 3 gene (either ts K or D30EBA) as helper virus. Cultured fibroblasts were infected with pHSVth and 1 day later tyrosine hydroxylase immunoreactivity and tyrosine hydroxylase enzyme activity were observed. The tyrosine hydroxylase enzyme activity directed the production of L-DOPA. pHSVth infection of striatal cells in dissociated cell culture resulted in expression of tyrosine hydroxylase RNA and tyrosine hydroxylase immunoreactivity. Release of L-DOPA and low levels of dopamine were observed from cells in pHSVth-infected striatal cultures. Expression of tyrosine hydroxylase and release of catecholamines were maintained for at least 1 week after infection.

Original languageEnglish
Pages (from-to)487-496
Number of pages10
JournalJournal of Neurochemistry
Volume64
Issue number2
StatePublished - Feb 1995

Keywords

  • Defective herpes simplex virus vector
  • Gene therapy
  • Parkinson's disease
  • Striatal neuron
  • Tyrosine hydroxylase

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