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Journal of Virology, October 2002, p. 10524-10529, Vol. 76, No. 20
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.20.10524-10529.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Evolutionary Dynamics of Viral Attenuation

Marty R. Badgett,1 Alexandra Auer,2 Leland E. Carmichael,2 Colin R. Parrish,2 and James J. Bull1*

Section of Integrative Biology and Institute for Cellular and Molecular Biology, University of Texas, Austin, Texas 78712-1023,1 James A. Baker Institute, College of Veterinary Medicine, Cornell University, Ithaca, New York 148532

Received 6 May 2002/ Accepted 19 July 2002

The genetic trajectory leading to viral attenuation was studied in a canine parvovirus (CPV) strain grown on dog kidney cells for 115 transfers. Consensus sequences of viral populations at passages 0, 3, 30, 50, 80, and 115 were obtained from PCR products covering 86% of the genome; clones from each of the 80th and 115th passages were also sequenced, covering 69% of the genome. Sixteen changes were fixed in the 115th-passage virus sample. Levels of polymorphism were strikingly different over time, in part because of a plaque-cloning step at passage 112 that reduced variation: passage 80 had 19 variants common among the clones, but passage 115 had only a single common variant. Several mutations increased in the culture at the same time, with most reaching fixation only after the 80th passage. The pattern of evolution was consistent with recombination and not with separate selective sweeps of individual mutations. Thirteen of the changes observed were identical to or at the same positions as changes observed in other isolates of CPV or feline panleukopenia virus.

* Corresponding author. Mailing address: Section of Integrative Biology and Institute for Cellular and Molecular Biology, University of Texas, Austin, TX 78712-1023. Phone: (512) 471-8266. Fax: (512) 471-3878. E-mail: bull{at}bull.biosci.utexas.edu.

Journal of Virology, October 2002, p. 10524-10529, Vol. 76, No. 20
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.20.10524-10529.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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