98. Acute Phase CTL Escape Is a Hallmark of Simian Immunodeficiency Virus Infection

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Session 24 Oral Abstract Session
Antiretroviral Chemotherapy: Pathogenesis of Primary HIV Infection
Session Time: Wednesday, 10 am - 12:30 pm
Room 6A-B

11:45 98.

Acute Phase CTL Escape Is a Hallmark of Simian Immunodeficiency Virus Infection
D. H. O’Connor*¹, T. M. Allen¹, T. U. Vogel¹, P. Jing¹, I. P. DeSouza¹, E. Dodds¹, E. J. Dunphy¹, C. Melsaether¹, B. Mothé¹, H. Horton¹, A. L. Hughes², and D. I. Watkins¹
¹Wisconsin Regional Primate Res. Ctr., Madison and ²Univ. of South Carolina, Columbia

Background: Human immunodeficiency viruses (HIV) and simian immunodeficiency viruses (SIV) escape from cytotoxic T-lymphocyte (CTL) recognition. Rapid emergence of escape variants during acute infection implies containment of wild-type virus replication by the CTL that recognize the escaping epitopes and is a measure of CTL efficacy in vivo.
Methods: To identify these effective CTL, we sequenced 21 complete SIVmac239 genomes at 4 weeks post-infection. We mapped CTL epitopes that rapidly selected for escape variants and characterized the ability of the responding CTL to be stimulated by different concentrations of peptide.
Results: We show that viruses from 19 of the 21 animals escaped from at least 1 CTL response during acute infection. This comprehensive analysis identified 7 acute-phase CTL responses, including the previously described Mamu-A*01-restricted Tat_28-35SL8 response. We mapped 3 of these CTL responses and showed that CTL responses that select for viral variants in the acute phase were more responsive to lower concentrations of peptide than CTL that did not select escape variants until late in infection.
Discussion: Previous studies have demonstrated that CTL that only require low peptide concentrations for stimulation (high functional avidity) are particularly effective at controlling viral infections. Our results suggest that acute viral escape from CTL is a hallmark of SIV infection and that CTL with high functional avidity rapidly select for these escape variants. These findings may have implications for the choice of epitopes that should be included in candidate HIV vaccines.