COMBINATION OF ANTIVIRAL IMMUNOTOXIN AND GANCICLOVIR OR CIDOFOVIR FORTHE TREATMENT OF MURINE CYTOMEGALOVIRUS INFECTIONS

Citation
Df. Smee et al., COMBINATION OF ANTIVIRAL IMMUNOTOXIN AND GANCICLOVIR OR CIDOFOVIR FORTHE TREATMENT OF MURINE CYTOMEGALOVIRUS INFECTIONS, Antiviral research, 32(3), 1996, pp. 165-171
Citations number
21
Categorie Soggetti
Virology
Journal title
ISSN journal
01663542
Volume
32
Issue
3
Year of publication
1996
Pages
165 - 171
Database
ISI
SICI code
0166-3542(1996)32:3<165:COAIAG>2.0.ZU;2-7
Abstract
The effects of two anti-murine cytomegalovirus (MCMV) immunotoxins use d in combination with ganciclovir (GVC) or cidofovir (HPMPC) against M CMV 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 th e initial infection rate. The immunotoxins (0.63, 1.25 and 2.5 mu g/ml ) combined with GCV (1.25, 2.5 and 5 mu M) or HPMPC (0.03, 0.06 and 0. 12 mu M) caused synergistic inhibition of virus yield in C127I cells a t most of the combinations tested. No toxic effect on cell growth in c ulture was observed at these immunotoxin/drug combinations. The effect s of immunotoxin and GCV treatment were studied further in MCMV-infect ed severe combined immunodeficient (SCID) mice. Immunotoxin (1 mg/kg p er day) given by intraperitoneal (i.p.) injection on days 1, 4 and 7 o f 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 7 days starting at 24 h after virus inoculation extended survival time almost 11 days. The combination of immunotoxin plus GCV was bette r than GCV alone, extending the mean day to death an additional 2 to 3 days, which is suggestive of a synergistic effect.