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

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.

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