Conditional CD8+T Cell Escape during Acute Simian Immunodeficiency Virus Infection

Abstract

CD8+ T cell responses rapidly select viral variants during acute human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) infection. We used pyrosequencing to examine variation within three SIV-derived epitopes (Gag₃₈₆₋₃₉₄GW9, Nef₁₀₃₋₁₁₁RM9, and Rev₅₉₋₆₈SP10) targeted by immunodominant CD8+ T cell responses in acutely infected Mauritian cynomolgus macaques. In animals recognizing all three epitopes, variation within Rev₅₉₋₆₈SP10 was associated with delayed accumulation of variants in Gag₃₈₆₋₃₉₄GW9 but had no effect on variation within Nef₁₀₃₋₁₁₁RM9. This demonstrates that the entire T cell repertoire, rather than a single T cell population, influences the timing of immune escape, thereby providing the first example of conditional CD8+ T cell escape in HIV/SIV infection.