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Journal of Virology, December 2004, p. 14012-14022, Vol. 78, No. 24
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.24.14012-14022.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

A Dominant Role for CD8+-T-Lymphocyte Selection in Simian Immunodeficiency Virus Sequence Variation{dagger}

David H. O'Connor,1 Adrian B. McDermott,1 Kendall C. Krebs,1 Elizabeth J. Dodds,1 Jacqueline E. Miller,1 Edna J. Gonzalez,1 Timothy J. Jacoby,1 Levi Yant,1 Helen Piontkivska,2 Ralph Pantophlet,3 Dennis R. Burton,3 William M. Rehrauer,1 Nancy Wilson,1 Austin L. Hughes,2 and David I. Watkins1*

Wisconsin Primate Research Center and Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, Wisconsin,1 Department of Biological Sciences, University of South Carolina, Columbia, South Carolina,2 The Scripps Research Institute, La Jolla, California3

Received 11 May 2004/ Accepted 4 August 2004

CD8+ T lymphocytes (CD8-TL) select viral escape variants in both human immunodeficiency virus and simian immunodeficiency virus (SIV) infections. The frequency of CD8-TL viral escape as well as the contribution of escape to overall virus diversification has not been assessed. We quantified CD8-TL selection in SIV infections by sequencing viral genomes from 35 SIVmac239-infected animals at the time of euthanasia. Here we show that positive selection for sequences encoding 46 known CD8-TL epitopes is comparable to the positive selection observed for the variable loops of env. We also found that >60% of viral variation outside of the viral envelope occurs within recognized CD8-TL epitopes. Therefore, we conclude that CD8-TL selection is the dominant cause of SIV diversification outside of the envelope.

* Corresponding author. Mailing address: Department of Pathology, University of Wisconsin, 1300 University Ave., Madison, WI 53706. Phone: (608) 265-3380. Fax: (608) 265-8084. E-mail: watkins{at}primate.wisc.edu.

{dagger} Supplemental material for this article may be found at http:://jvi.asm.org/.

Journal of Virology, December 2004, p. 14012-14022, Vol. 78, No. 24
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.24.14012-14022.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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