Combination of antiviral immunotoxin and ganciclovir or cidofovir for the treatment of murine cytomegalovirus infections.
The effects of two anti-murine cytomegalovirus (MCMV) immunotoxins used in combination with ganciclovir (GCV) or cidofovir (HPMPC) against MCMV were determined in vitro and in mice. The inhibitors were added to cell cultures 24 or 48 h after MCMV adsorption so as to not affect the initial infection rate. The immunotoxins (0.63, 1.25 and 2.5 micrograms/ml) combined with GCV (1.25, 2.5 and 5 microM) or HPMPC (0.03, 0.06 and 0.12 microM) caused synergistic inhibition of virus yield in C127I cells at most of the combinations tested. No toxic effect on cell growth in culture was observed at these immunotoxin/drug combinations. The effects of immunotoxin and GCV treatment were studied further in MCMV-infected severe combined immunodeficient (SCID) mice. Immunotoxin (1 mg/kg per day) given by intraperitoneal (i.p.) injection on days 1, 4 and 7 of the infection did not extend the mean day to death compared with the placebo group. Once daily i.p. treatment with GCV (50 mg/kg per day) for days starting at 24 h after virus inoculation extended survival time almost 11 days. The combination of immunotoxin plus GCV was better than GCV alone, extending the mean day to death an additional 2 to 3 days, which is suggestive of a synergistic effect.
Smee
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DF
Institute for Antiviral Research, Utah State University, Logan 84322-5600, USA.
Sidwell
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RW
Barnett
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D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D000077404:Cidofovir; D003586:Cytomegalovirus Infections / Q000188:drug therapy / Q000821:virology*; D003596:Cytosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004359:Drug Therapy, Combination; D015774:Ganciclovir / Q000494:pharmacology*; D000922:Immunotoxins / Q000494:pharmacology*; D051379:Mice; D016513:Mice, SCID; D018146:Muromegalovirus / Q000187:drug effects* / Q000254:growth & development; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D010940:Plant Proteins / Q000494:pharmacology*; D054789:Ribosome Inactivating Proteins, Type 1; D012276:Ricin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000998:Antiviral Agents; D000922:Immunotoxins; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D010940:Plant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; C025674:GEL protein, Gelonium multiflorum; D003596:Cytosine; D012276:Ricin; D000077404:Cidofovir; D015774:Ganciclovir