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Journal of Virology, May 2001, p. 4439-4443, Vol. 75, No. 9
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.9.4439-4443.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Generation of a Highly Pathogenic Avian Influenza A Virus from an Avirulent Field Isolate by Passaging in Chickens

Toshihiro Ito,^1,* Hideo Goto,² Eiji Yamamoto,¹ Hiroko Tanaka,¹ Mutsuko Takeuchi,¹ Masaru Kuwayama,¹ Yoshihiro Kawaoka,^2,3 and Koichi Otsuki¹

Department of Veterinary Public Health, Faculty of Agriculture, Tottori University, Tottori 680-8553,¹ and Institute of Medical Science, University of Tokyo, Tokyo 108-8639,³ Japan, and Department of Pathobiological Sciences, School of Veterinary Medicine, University of WisconsinMadison, Madison, Wisconsin 53706²

Received 16 October 2000/Accepted 13 February 2001

Highly virulent avian influenza viruses can arise from avirulent strains maintained in poultry, but evidence to support their generation from viruses in wild birds is lacking. The most likely mechanism for the acquisition of virulence by benign avian viruses is the introduction of mutations by error-prone RNA polymerase, followed by the selection of virulent viruses. To investigate whether this mechanism could apply to wild waterfowl, we studied an avirulent wild-swan virus that replicates poorly in chickens. After 24 consecutive passages by air sac inoculation, followed by five passages in chicken brain, the avirulent virus became highly pathogenic in chickens, producing a 100% mortality rate. Sequence analysis at the hemmaglutinin cleavage site of the original isolate revealed a typical avirulence type of sequence, R-E-T-R, which progressed incrementally to a typical virulence type of sequence, R-R-K-K-R, during repeated passages in chickens. These results demonstrate that avirulent viruses maintained in wild waterfowl in nature and bearing the consensus avirulence type sequence R-E-T-R have the potential to become highly pathogenic while circulating in chickens.

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^* Corresponding author. Mailing address: Department of Veterinary Public Health, Faculty of Agriculture, Tottori University, Tottori 680-8553, Japan. Phone: 81-857-31-5437. Fax: 81-857-31-5437. E-mail: toshiito{at}muses.tottori-u.ac.jp.

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Journal of Virology, May 2001, p. 4439-4443, Vol. 75, No. 9
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.9.4439-4443.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

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