Selective cytotoxicity towards cytomegalovirus-infected cells by immunotoxins consisting of gelonin linked to anti-cytomegalovirus 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 immunoglobulin (IgG). In uninfected cells, there was no difference between [35S]methionine incorporation in untreated cultures and those treated with immunotoxin at 100 micrograms/ml. In HCMV-infected cells, there was a significant decrease in [35S]methionine incorporation in the immunotoxin-treated cultures, suggesting a selective cytotoxic effect on the virus-infected cells. An immunotoxin specific for murine cytomegalovirus (MCMV) was prepared by linking gelonin to polyclonal anti-MCMV IgG. Using this same parameter for assay of cytotoxicity, the anti-MCMV immunotoxin had a 50% cytotoxic concentration of 35 micrograms/ml in MCMV-infected cells and greater than 200 micrograms/ml in uninfected cells. MCMV yields measured at 7 days postinoculation were reduced by 2 log10 in cultures treated with immunotoxin at 20 micrograms/ml at 1 day postinoculation. These data suggest immunotoxins may have potential for eliminating CMV-infected cells from the host.
Barnett
B B
BB
Institute for Antiviral Research, Utah State University, Logan 84322-5500, USA.
Smee
D F
DF
Malek
S M
SM
Sidwell
R W
RW
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology / Q000494:pharmacology*; D002460:Cell Line; D003587:Cytomegalovirus / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000494:pharmacology; D000922:Immunotoxins / Q000494:pharmacology*; D008715:Methionine / Q000493:pharmacokinetics*; D051379:Mice; D018146:Muromegalovirus / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D010940:Plant Proteins / Q000494:pharmacology*; D054789:Ribosome Inactivating Proteins, Type 1
D000914:Antibodies, Viral; D007074:Immunoglobulin G; D000922:Immunotoxins; D010940:Plant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; C025674:GEL protein, Gelonium multiflorum; D008715:Methionine