Effect of Cytosine Arabinoside and 5-Iodo-2′-Deoxyuridine on a Cytomegalovirus Infection in Newborn Mice

Self Cite

mentioning

confidence: 99%

Treatment of a Murine Cytomegalovirus Infection with Exogenous Interferon, Polyinosinic-Polycytidylic Acid, and Polyinosinic-Polycytidylic Acid–Poly- l -Lysine Complex

Kern

Olsen

Overall

et al. 1978

Self Cite

“…The cells were trypsinized, and trypan blueexcluding cells were counted. MEF cultures grown in 1 or 10 ,uM TFT yielded 24 or 33% fewer cells, respectively, compared with controls. HFF cultures grown in 1 or 10,uM TFT yielded 16 or 59% fewer cells, respectively, compared with controls.…”

Section: Methodsmentioning

confidence: 99%

Activity of trifluorothymidine against cytomegalovirus

Wingard¹,

Stuart²,

Saral³

et al. 1981

Trifluorothymidine (TFT) was tested for antiviral activity against mouse cytomegalovirus (MCMV) and human cytomegalovirus (HCMV) Trifluorothymidine (TFT) is a thymidine analog developed in the search for fluorinated pyrimidines with antineoplastic activity (16). After phosphorylation by thymidine kinase (TK), TFT has been shown to inhibit deoxyribonucleic acid (DNA) polymerase (32), to be incorporated into DNA (15, 16), and to inhibit thymidylate synthetase (31). Antiviral activity against bacteriophage T4 (16), vaccinia virus (1, 33), and herpes simplex virus (HSV) type 1 (1, 6, 9) has been demonstrated. This communication reports the antiviral activity of TFT against mouse cytomegalovirus (MCMV) and human cytomegalovirus (HCMV). MATERIALS AND METHODSVirus. The Smith strain of MCMV (ATCC MCMV assays were performed by adsorbing 0.1-ml portions of serially diluted samples in quadruplicate onto confluent MEF monolayers in TC-24 (Costar) 16-mm wells. After 1 h, unadsorbed virus was aspirated, the monolayers were overlaid with 0.9% methylcellulose containing minimal essential medium (with Earle salts), 5% NCS, 15 mM N-2-hydroxyethylpiperazine-N-2'-ethanesulfonic acid (HEPES) buffer, and gentamicin (35 ug/ml), and the cultures were incubated at 37°C in 5% CO2. After 6 days the overlays were removed, and the monolayers were fixed in absolute ethanol before staining with 0.5% methylene blue and counting plaques. HCMV assays were performed by adsorbing 0.025-ml portions of serially diluted samples onto HFF monolayers in TC96 (Costar) 6.4-mm wells.After 1 h, unadsorbed virus was aspirated, medium was added, and the monolayers were incubated for 25 days and examined twice weekly for the presence of cytopathic effect. The 50% inhibitory dose (ID5o)

“…Recently, Kelsey et al (6) examined the effects of cytosine arabinoside and 5-iodo-2'-deoxyuridine on MCMV. Both drugs inhibited MCMV in cell culture, but neither affected the lethal outcome of disseminated MCMV infection in suckling mice, even at doses that were lethal for a proportion of drug-treated controls.…”

Section: Discussionmentioning

confidence: 99%

“…In animal systems, ribavirin demonstrated activity against influenza A and B (7), vaccinia (15), and herpes simplex (15) infections. The infection in mice produced by MCMV is well characterized (10,11,20) and has been used as a model to evaluate the effectiveness of chemotherapeutic agents (6). This work examines the activity of ribavirin against MCMV in cell culture and in mice.…”

mentioning

confidence: 99%

Effect of Ribavirin on Murine Cytomegalovirus Infection

Dowling

Postic

Guevarra

1976

Ribavirin (1-,8-D-ribofuranosyl-1,2,4-triazole-3-carboxamide), a new synthetic nucleoside, inhibited murine cytomegalovirus in cell culture. This was shown by the inhibition of viral cytopathic effect and plaque formation, as well as reduction in the yield of virus. Despite this in vitro antiviral effect, ribavirin did not protect mice from mortality produced by a high inoculum of cytomegalovirus. When a lower inoculum was used to initiate a chronic infection, the administration of ribavirin for 9 days had no effect on the titer of cytomegalovirus in the salivary gland, kidney, liver, and spleen. Thus, ribavirmin was ineffective in the treatment of both acute and chronic murine cytomegalovirus infections.Cytomegalovirus causes a broad spectrum of clinical illnesses including congenital infection, the mononucleosis syndrome, and involvement of various organs in immunosuppressed hosts (18). Human cytomegaloviruses (HCMV) are inhibited by the nucleoside analogues adenine arabinoside, cytosine arabinoside, and 5-iodo-2'-deoxyuridine in cell culture (4). In clinical trials, these antiviral agents may transiently suppress urinary excretion of HCMV, but generally fail to eradicate the virus or alter the natural course of disease (2,3,8,9,13). The search for antiviral agents capable of inhibiting HCMV should therefore be continued.Rivavirin (1-,3-D-ribofuranosyl-1,2,4-triazole-3-carboxamide) is a new synthetic nucleoside which is active in cell culture against numerous deoxyribonucleic acid and ribonucleic acid viruses (5). The in vitro inhibition of herpesviruses, including murine cytomegalovirus (MCMV), by ribavirin has compared favorably with other antiviral compounds (5,14,19). In animal systems, ribavirin demonstrated activity against influenza A and B (7), vaccinia (15), and herpes simplex (15) infections. The infection in mice produced by MCMV is well characterized (10,11,20) and has been used as a model to evaluate the effectiveness of chemotherapeutic agents (6). This work examines the activity of ribavirin against MCMV in cell culture and in mice. The antiviral effect in cultured cells was first determined by three methods. Then, ribavirin was evaluated in both acute, lethal and chronic, subclinical murine infections. Cell culture. MCMV was grown in secondary mouse embryo tissue culture (METC) maintained with medium 199 supplemented with 2% newborn calf serum, 0.2% NaHCO3, penicillin (100 U/ml), streptomycin (100 ,.tg/ml), and nystatin (50 U/ml). Titration was carried out in METC by the plaquing method using tragacanth overlay (12). After 7 days, the tragacanth was removed and the cell sheets were stained with a dye-fixer solution containing 0.5% methylrosaniline chloride, 5% formalin (vol/ vol), 50%o ethanol (vol/vol), and 0.85% NaCl in distilled water (1). Plaques were enumerated with the aid of a dissecting microscope.Ribavirin. Ribavirin was kindly supplied by Robert W. Sidwell (ICN Nucleic Acid Research Institute, Irvine, Calif.). CPE inhibition. MCMV was added to METC in tube cultures. After virus adsorp...