SELECTIVE CYTOTOXICITY TOWARDS CYTOMEGALOVIRUS-INFECTED CELLS BY IMMUNOTOXINS CONSISTING OF GELONIN LINKED TO ANTICYTOMEGALOVIRUS ANTIBODY

An immunotoxin specific for cells infected with human cytomegalovirus (HCMV) was constructed by attaching the ribosome-inactivating enzyme, gelonin, through a disulfide linkage to polyclonal human immunoglobuli n (IgG). In uninfected cells, there was no difference between [S-35]me thionine incorporation in untreated cultures and those treated with im munotoxin at 100 mu g/ml. In HCMV-infected cells, there was a signific ant decrease in [S-35]methionine incorporation in the immunotoxin-trea ted cultures, suggesting a selective cytotoxic effect on the virus-inf ected cells. An immunotoxin specific for murine cytomegalovirus (MCMV) was prepared by linking gelonin to polyclonal anti-MCMV IgG. Using th is same parameter for assay of cytotoxicity, the anti-MCMV immunotoxin had a 50% cytotoxic concentration of 35 mu g/ml in MCMV-infected cell s and greater than 200 mu g/ml in uninfected cells. MCMV yields measur ed at 7 days postinoculation were reduced by 2 log(10) in cultures tre ated with immunotoxin at 20 mu g/ml at 1 day postinoculation. These da ta suggest immunotoxins may have potential for eliminating CMV-infecte d cells from the host.