title: The effect of herpes simplex virus virion host shutoff gene- a new suicide gene- on tumor cells.
abstract: The herpes simplex virus (HSV) UL41 gene product, virion host shutoff (Vhs) protein, mediates the rapid degradation of both viral and cellular mRNA. This ability suggests that Vhs protein can be used as a suicide gene in cancer gene therapy applications. The recent reports have shown that the degradation of cellular mRNA during herpes simplex infection is selective. RNA containing AU-rich elements (ARE) in their 3' untranslated ends are the targets for the Vhs protein. RNA that are not subject to Vhs protein-dependent degradation are up-regulated during HSV infection. ARE are frequently found in mRNA that encode proto-oncogenes, nuclear transcription factors, and cytokines. In many human cancers, the AU-rich stretch of proto-oncogenes and regulatory genes has impaired.
  
  
  
  To investigate whether Vhs protein might be useful for inhibition of tumor cell proliferation, a eukaryotic expression vector containing Vhs protein gene was constructed. Cell degradation and RNA content of HeLa and MRC-5 tumor cells after transfection with the constructed vector were studied.
  
  
  
  The results showed a strong inhibitory activity in proliferation of transfected tumor cells and a sharp decrease in their RNA content.
  
  
  
  These data suggest that Vhs protein can be considered as a candidate for suicide cancer gene therapy.
authors.affiliation: Dept of Virology, School of Medical Sciences, Tarbiat Modarres University, Tehran, Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Bannazadeh Baghi
authors.affiliation: Dept of Virology, School of Medical Sciences, Tarbiat Modarres University, Tehran, Iran.
authors.forename: Taravat
authors.initials: T
authors.lastname: Bamdad
authors.affiliation: Dept of Virology, School of Medical Sciences, Tarbiat Modarres University, Tehran, Iran.
authors.forename: Hoorieh
authors.initials: H
authors.lastname: Soleimanjahi
mesh_terms: D000818:Animals; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D041722:Genes, Transgenic, Suicide / Q000235:genetics / Q000502:physiology*; D015316:Genetic Therapy; D006367:HeLa Cells; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D020871:RNA Stability / Q000235:genetics; D012260:Ribonucleases; D018139:Simplexvirus / Q000235:genetics; D014407:Tumor Cells, Cultured; D014709:Vero Cells; D014764:Viral Proteins / Q000235:genetics* / Q000502:physiology*; D001613:beta 2-Microglobulin / Q000235:genetics / Q000378:metabolism
chemical_list: D014764:Viral Proteins; D001613:beta 2-Microglobulin; C070722:virion host shutoff protein, Simplexvirus; D012260:Ribonucleases