Differential response of ferrets to infection with virulent and avirulent influenza viruses: A possible marker of virus attenuation

Summary

The behaviour of three recombinant strains of influenza virus A/England/939/69 and A/PR/8, together with the parent A/England/939/69 strain, all of known virulence to man, were examined in ferrets. For the virulent A/England/939/69 strain, the peak temperature response and the time of peak virus excretion occurred 48 hours post-infection, and peak protein and secretory antibody responses occurred on days 7 and 9. In contrast, the peak temperatures and maximum virus excretions for the recombinant attenuated viruses, clones 7 and 6a, occurred on day 3 and 6, and the maximum protein and nasal antibody responses on days 9 and 11, respectively. Although the peak responses for these strains were distinct, the magnitudine of the symptoms was comparable. Similar studies with the over attenuated clone 64C virus showed a milder infection. In addition, the maximum temperature response and virus excretion occurred on day 5 post-infection, and the maximum nasal protein concentration was found on day 11 after virus infection. These differences between the strains were only apparent when animals were given an inoculum of 10 EID₅₀; no differences were observed between the four strains when larger inocula were used. The results suggest that virus infection of ferrets was distinct for strains of differing human virulence, and that the ferret model may provide a test for virulence for man.