Expression of the bcl-2 gene from a defective HSV-1 amplicon vector protects pancreatic β-cells from apoptosis

Yingxian Liu, Alex Rabinovitch, Wilma Suarez-Pinzon, Bhaskar Muhkerjee, Michael Brownlee, Diane Edelstein, Howard J. Federoff

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Abstract

It has been suggested that the mechanism of pancreatic β-cell death in autoimmune diabetes mellitus and in immunoisolated transplantation devices involves cytokine-induced apoptosis. To explore the feasibility of a gene transfer strategy to protect β-cells, we evaluated the use of replication defective HSV-1 amplicon vectors as gene transfer vehicles. Post-mitotic murine and human β-cells were efficiently transduced by a herpes simplex virus (HSV) vector that expresses the reporting gene Escherichia coli lacZ under the transcriptional control of a HSV promoter (HSVlac) both as islets and as single cells. Insulin secretion, a marker of β-cell function, was unaffected by HSVlac transduction of a β-cell line. A HSV amplicon vector that expressed bcl-2 (HSVbcl2) in β-cells was constructed, and its effects on cytokine-mediated apoptosis in both a β-cell line and primary murine β-cells assessed by measuring internucleosomal fragmentation. β-Cell apoptosis was blocked by transduction with HSVbcl2 but not HSVlac. The prevention of cytokine-induced apoptosis in β-cells by bcl-2 expression has the potential both to ameliorate primary autoimmune β-cell destruction as type I diabetes develops, and to prevent the destruction of transplanted β-cells inside immunoisolation devices.

Original languageEnglish (US)
Pages (from-to)1719-1726
Number of pages8
JournalHuman Gene Therapy
Volume7
Issue number14
DOIs
Publication statusPublished - Sep 10 1996

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ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

Liu, Y., Rabinovitch, A., Suarez-Pinzon, W., Muhkerjee, B., Brownlee, M., Edelstein, D., & Federoff, H. J. (1996). Expression of the bcl-2 gene from a defective HSV-1 amplicon vector protects pancreatic β-cells from apoptosis. Human Gene Therapy, 7(14), 1719-1726. https://doi.org/10.1089/hum.1996.7.14-1719