Effect of Ribavirin on Influenza Virus Infection in Ferrets
The effect of 1- -ribofuranosyl-2, 4-triazole-3-carboxamide (ribavirin) on influence virus infection was studied in ferrets. Ferrets were given 100 mg/kg of ribavirin intraperitoneally one day before and 1 and 24 hrs following intranasal infection with 103.0 ferret infective doses of A/Port Chalmers/73 virus. Ribavirin caused a reduction in the febrile response, and the peak temperature reaction occurred 24 hrs later than for control animals. Drug-treated ferrets produced both nasal wash antibody and increased levels of protein, but the peak levels, similar to those of control ferrets, occurred later than in untreated animals. Titres of virus isolated from nasal washings were similar for the two groups, but peak titres occurred later after infection in treated ferrets.
The response of ferrets to influenza infection was also examined in animals given ribavirin one day before, one hr before and daily for five days after virus infection. These animals showed no temperature response, no increase of nasal wash protein and did not produce nasal antibody following virus infection. In addition, drug-treated ferrets had markedly reduced titres of virus in nasal washings, and did not produce serum antibody following virus infection. The absence of an antibody response was probably due to the immunosuppressive action of the compound.
The compound 1- -D Ribofuranosyl-1, 2, 4-triazole-3-carbox-amide (Ribavirin) has been reported to inhibit the replication of a number of DNA and RNA viruses (Sidwell et al, 1972- Witkowski et al, 1972- Huffman et al, 1973); specifically, ribavirin was found to inhibit influenza virus infection in vitro (Huffman et al, 1973; Todo, 1973; Oxford, 1975) and in vivo (Sidwell et al, 1972; Khare et al, 1973). In the present study, the effects of ribavirin on influenza virus A/Port Chalmers/73 infection of ferrets was examined, since influenza in these species closely approximates the disease in man)Smith et al, 1933; Haff et al, 1966; Potter et al, 1972) and this recommends the ferret for the investigation of influenza inhibiting compounds. Thus, ferrets infected with influenza viruses show a sharp febrile response, produce high titres of virus, produce nasal wash and serum antibody and show a marked increase in nasal wash protein (Smith et al, 1933; Francis and Stuart-Harris, 1938; Lui, 1955; Haff et al, 1966). Using these parameters, the effects of antiviral compounds on influenza virus infection can be measured qualitatively (Cochran et al, 1965; Squires, 1970; Potter et al, 1972; Haff and Pinto, 1973; Potter and Schofield, 1975).
KeywordsInfluenza Virus Haemagglutination Inhibition Influenza Virus Infection Influenza Virus Vaccine Nasal Washing
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