Tat-Specific CTL Responses Select for Escape Variants During Acute SIV Infection

Todd M. Allen*‡, David H. O’Connor*‡, Peicheng Jing*, John L. Dzuris§, Bianca R. Mothé*, Ed Dunphy*, Max E. Liebl*, Thorsten U. Vogel*, Carol Emerson*, Nancy Wilson*, Kevin J. Kunstman#, Xiaochi Wang||, Austin L. Hughes· , Ronald C. Desrosiers+, John D. Altman||, Steven M. Wolinsky#, Alessandro Sette§, David I. Watkins*¶**

*Wisconsin Regional Primate Research Center, University of Wisconsin, Madison, WI 53715-1299, USA, §Epimmune, San Diego, CA 92121, USA, #Northwestern University Medical School, Chicago, IL 60611-3008, USA, ||Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA, · Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, USA, +New England Regional Primate Research Center, Southborough, MA 01772-9102, USA, Dept. of Pathology and Laboratory Medicine, University of Wisconsin, Madison, WI 53706-1532, USA, [**To whom correspondence should be addressed: Phone: (608)-265-3380; FAX: (608)-262-5494]

Strong cytotoxic T lymphocyte (CTL) responses emerge early in HIV and SIV infections coincident with declining plasma viremia. Here we show that this initial CTL response selects for viral escape variants within an immunodominant Tat epitope. By eight weeks post-infection, the majority of the replicating virus escapes recognition by these CTL. In contrast, no variation occurs in three other previously identified CTL epitopes in Gag, Env, and Vif. These findings imply that replication of wild-type virus is initially controlled by Tat-specific CTL and suggests that induction of CTL active during acute viremia might be an important component of an effective HIV vaccine.

‡TMA and DHO contributed equally to this work.

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