Effect of Ribavirin on Murine Cytomegalovirus Infection

Abstract

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...

Toxicologic effects of ribavirin in cats

“…FeLV infection, feline infectious peritonitis), which may themselves induce bone marrow hypoplasia, thrombocytopenia, or haemorrhagic diathesis, may be outweighed by the drug's toxicity. Indeed, ribavirin toxicity can exacerbate lesions and disease induced by viruses, as reported in mice infected with cytomegalovirus (Dowling et al, 1976) or cats infected with FCV (Povey, 1978b) or feline infectious peritonitis virus (Weiss et al, in press).…”

Spectroscopic (FT-IR, FT-Raman) investigation, topology (ESP, ELF, LOL) analyses, charge transfer excitation and molecular docking (dengue, HCV) studies on ribavirin

“…An ab-initio method has been followed to study the derivatives of triazoles [6][7][8] . Since the first report of the broad spectrum antiviral activity and synthesis of ribavirin [9,10] , the in vitro and in vivo antiviral activity has been confirmed in many independent laboratories [11][12][13][14][15][16][17] . Ribavirin has been proved clinically effective against hepatitis A virus [18][19][20] .…”