title: GADD34 gene restores virulence in viral vector used in experimental stroke study.
abstract: GADD34 is expressed in the ischaemic brain and reverses protein synthesis shutdown. Consequently, GADD34 could have neuroprotective potential in stroke. BHK medium, a replication-deficient HSV viral vector (HSV1716) with no insert or containing full-length GADD34, the N terminal or a conserved portion of the gene, was injected into mouse brain before stroke. Infarct size was 1.0+/-0.26, 1.19+/-0.36, 1.5+/-0.36, 1.3+/-0.36, and 1.1+/-0.28 mm3, respectively. The increase in infarct size with full-length GADD34 was statistically significant (P<0.05). Immunohistochemistry confirmed viral protein expression. Tissue culture studies revealed GADD34 gene restored virulence in HSV1716, suggesting that HSV virulence, rather than increased GADD34, exacerbated ischaemic damage.
authors.affiliation: Division of Clinical Neuroscience, Wellcome Surgical Institute, Garscube Estate, University of Glasgow, Glasgow, UK. cmc39v@clinmed.gla.ac.uk
authors.forename: Christopher
authors.initials: C
authors.lastname: McCabe
authors.forename: Fiona
authors.initials: F
authors.lastname: White
authors.forename: S Moira
authors.initials: SM
authors.lastname: Brown
authors.forename: I Mhairi
authors.initials: IM
authors.lastname: Macrae
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics*; D020520:Brain Infarction / Q000473:pathology / Q000821:virology; D002545:Brain Ischemia / Q000473:pathology / Q000821:virology*; D018797:Cell Cycle Proteins / Q000235:genetics*; D004195:Disease Models, Animal; D005822:Genetic Vectors / Q000009:adverse effects*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D054645:Protein Phosphatase 1; D018139:Simplexvirus / Q000472:pathogenicity* / Q000502:physiology; D020521:Stroke / Q000150:complications / Q000473:pathology / Q000821:virology*; D014774:Virulence
chemical_list: D000943:Antigens, Differentiation; D018797:Cell Cycle Proteins; C513256:Ppp1r15a protein, mouse; D054645:Protein Phosphatase 1