GADD34 gene restores virulence in viral vector used in experimental stroke study.
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.
McCabe
Christopher
C
Division of Clinical Neuroscience, Wellcome Surgical Institute, Garscube Estate, University of Glasgow, Glasgow, UK. cmc39v@clinmed.gla.ac.uk
White
Fiona
F
Brown
S Moira
SM
Macrae
I Mhairi
IM
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
D000943:Antigens, Differentiation; D018797:Cell Cycle Proteins; C513256:Ppp1r15a protein, mouse; D054645:Protein Phosphatase 1