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
StatePublished - Sep 10 1996

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Defective Viruses
bcl-2 Genes
Human Herpesvirus 1
Apoptosis
Simplexvirus
Cytokines
Type 1 Diabetes Mellitus
Genes
Cell Line
Equipment and Supplies
Diabetes Mellitus
Cell Death
Transplantation
Insulin
Escherichia coli

ASJC Scopus subject areas

  • 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.

Expression of the bcl-2 gene from a defective HSV-1 amplicon vector protects pancreatic β-cells from apoptosis. / Liu, Yingxian; Rabinovitch, Alex; Suarez-Pinzon, Wilma; Muhkerjee, Bhaskar; Brownlee, Michael; Edelstein, Diane; Federoff, Howard J.

In: Human Gene Therapy, Vol. 7, No. 14, 10.09.1996, p. 1719-1726.

Research output: Contribution to journalArticle

Liu, Y, Rabinovitch, A, Suarez-Pinzon, W, Muhkerjee, B, Brownlee, M, Edelstein, D & Federoff, HJ 1996, 'Expression of the bcl-2 gene from a defective HSV-1 amplicon vector protects pancreatic β-cells from apoptosis', Human Gene Therapy, vol. 7, no. 14, pp. 1719-1726.
Liu Y, Rabinovitch A, Suarez-Pinzon W, Muhkerjee B, Brownlee M, Edelstein D et al. Expression of the bcl-2 gene from a defective HSV-1 amplicon vector protects pancreatic β-cells from apoptosis. Human Gene Therapy. 1996 Sep 10;7(14):1719-1726.
Liu, Yingxian ; Rabinovitch, Alex ; Suarez-Pinzon, Wilma ; Muhkerjee, Bhaskar ; Brownlee, Michael ; Edelstein, Diane ; Federoff, Howard J. / Expression of the bcl-2 gene from a defective HSV-1 amplicon vector protects pancreatic β-cells from apoptosis. In: Human Gene Therapy. 1996 ; Vol. 7, No. 14. pp. 1719-1726.
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