A dominant role for CD8 T lymphocyte selection in simian immunodeficiency virus sequence variation
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.
O'Connor DH, McDermott AB, Krebs KC, Dodds EJ, Miller JE, Gonzalez EJ, Jacoby TJ, Yant L, Piontkivska H, Pantophlet R, Burton DR, Rehrauer WM, Wilson N, Hughes AL, Watkins DI
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