|Budget Amount *help
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1999: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1998: ¥2,700,000 (Direct Cost: ¥2,700,000)
Although highly virulent avian influenza viruses in poultry are thought to arise from avirulent viruses maintained in wild birds, there is no direct evidence supporting this notion. In addition, the precise mechanism by which virus become pathogenic remains unknown. Most possible mechanism for this change is the introduction of mutation by error-prone RNA polymerase, followed by the selection of virulent viruses. To investigate whether this selective mechanism exists in chickens, we passaged in chicken an avirulent virus isolate from wild waterfowl, that poorly replicate in chickens. After 24 consecutive passages by air sac inoculation, followed by 5 passages in brain of chicks, the avirulent virus became highly pathogenic in chickens with 100% mortality rate. Sequence analysis at the hemmaglutinin (HA) cleavage site showed that the original isolate contained the typical avirulent type sequence, R-E-T-R, and during passages in chickens, the sequence step wisely changed to a typical virulent type, i.e., R-R-K-K-R. These results demonstrated that avirulent viruses maintained in wild waterfowl in nature, bearing the consensus avirulent type sequence, R-E-T-R, have a potential to become highly pathogenic viruses. These findings also indicated that a mechanism exist in chickens that select highly pathogenic derivatives from non-pathogenic precursors.