Expression of a viral gene in insulin-producing cell lines renders them susceptible to immunological destruction.
The gene coding for the glycoprotein D of herpes simplex virus type 1 was cloned into plasmids under the transcriptional control of the SV40 promoter-enhancer or the rat insulin 1 promoter-enhancer sequences. These plasmids were transfected into rat insulinoma cells (RINm5F) and mouse NIH/3T3 cells and the expression of glycoprotein D was examined using cell surface immunofluoresence. The rat insulin 1 promoter-enhancer sequences directed efficient expression in RINm5F cells, but not in NIH/3T3 cells. In contrast, the SV40 promoter-enhancer sequences worked well in NIH/3T3 cells, but not in RINm5F cells. Expression of glycoprotein D did not interfere with insulin production by RINm5F cells. When stable cel lines expressing glycoprotein D were exposed to anti-herpes simplex virus type 1 antibodies and complement, they were destroyed. These studies provide additional evidence that specific promoter-enhancer elements are required for efficient gene expression in certain cell types and demonstrate that the expression of foreign antigens on the surface of insulin-producing cells can lead to their immunological destruction.
Shibata
M
M
Laboratory of Oral Medicine, National Institute of Dental Research, Bethesda, Maryland.
Puga
A
A
Salata
K F
KF
Bachurski
C J
CJ
Lerman
M I
MI
Notkins
A L
AL
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D005814:Genes, Viral; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007340:Insulinoma / Q000276:immunology; D051379:Mice; D010190:Pancreatic Neoplasms / Q000276:immunology; D010957:Plasmids; D051381:Rats; D015183:Restriction Mapping; D018139:Simplexvirus / Q000235:genetics*; D014162:Transfection; D014759:Viral Envelope Proteins / Q000235:genetics*; D015678:Viral Structural Proteins / Q000235:genetics*
D007328:Insulin; D014759:Viral Envelope Proteins; D015678:Viral Structural Proteins; C039447:glycoprotein D, Human herpesvirus 1