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Journal of Virology, September 2004, p. 9652-9665, Vol. 78, No. 18
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.18.9652-9665.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Genetic Relationships and Evolution of Genotypes of Yellow Fever Virus and Other Members of the Yellow Fever Virus Group within the Flavivirus Genus Based on the 3' Noncoding Region

John-Paul Mutebi,1 René C. A. Rijnbrand,2 Heiman Wang,1 Kate D. Ryman,3 Eryu Wang,1 Lynda D. Fulop,4 Rick Titball,4 and Alan D. T. Barrett1*

Center for Biodefense and Emerging Infectious Diseases and Department of Pathology,1 Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas,2 Department of Microbiology and Immunology, Louisiana State University, Shreveport, Louisiana,3 Defence Science and Technology Laboratory, Porton Down, Salisbury, United Kingdom4

Received 19 August 2003/ Accepted 11 May 2004

Genetic relationships among flaviviruses within the yellow fever (YF) virus genetic group were investigated by comparing nucleotide sequences of the 3' noncoding region (3'NCR). Size heterogeneity was observed between members and even among strains of the same viral species. Size variation between YF strains was due to duplications and/or deletions of repeated nucleotide sequence elements (RYF). West African genotypes had three copies of the RYF (RYF1, RYF2, and RYF3); the Angola and the East and Central African genotypes had two copies (RYF1 and RYF3); and South American genotypes had only a single copy (RYF3). Nucleotide sequence analyses suggest a deletion within the 3'NCR of South American genotypes, including RYF1 and RYF2. Based on studies with the French neurotropic vaccine strain, passage of a YF virus strain in cell culture can result in deletion of RYF1 and RYF2. Taken together, these observations suggest that South American genotypes of YF virus evolved from West African genotypes and that the South American genotypes lost RYF1 and RYF2, possibly in a single event. Repeated sequence elements were found within the 3'NCR of other members of the YF virus genetic group, suggesting that it is probably characteristic for members of the YF virus genetic group. A core sequence of 15 nucleotides, containing two stem-loops, was found within the 3'NCR of all members of the YF genetic group and may represent the progenitor repeat sequence. Secondary structure predictions of the 3'NCR showed very similar structures for viruses that were closely related phylogenetically.

* Corresponding author. Mailing address: Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555-0609. Phone: (409) 772 6662. Fax: (409) 772-2500. E-mail: abarrett{at}utmb.edu.

Journal of Virology, September 2004, p. 9652-9665, Vol. 78, No. 18
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.18.9652-9665.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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