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