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CD8+ lymphocytes do not impact SIV reservoir establishment under ART

Statzu, M;Jin, W;Fray, EJ;Wong, AKH;Kumar, MR;Ferrer, E;Docken, SS;Pinkevych, M;McBrien, JB;Fennessey, CM;Keele, BF;Liang, S;Harper, JL;Mutascio, S;Franchitti, L;Wang, H;Cicetti, D;Bosinger, SE;Carnathan, DG;Vanderford, TH;Margolis, DM;Garcia-Martinez, JV;Chahroudi, A;Paiardini, M;Siliciano, J;Davenport, MP;Kulpa, DA;Siliciano, RS;Silvestri, G;

Persistence of the human immunodeficiency virus type-1 (HIV-1) latent reservoir in infected individuals remains a problem despite fully suppressive antiretroviral therapy (ART). While reservoir formation begins during acute infection, the mechanisms responsible for its establishment remain unclear. CD8+ T cells are important during the initial control of viral replication. Here we examined the effect of CD8+ T cells on formation of the latent reservoir in simian immunodeficiency virus (SIV)-infected macaques by performing experimental CD8+ depletion either before infection or before early (that is, day 14 post-infection) ART initiation. We found that CD8+ depletion resulted in slower decline of viremia, indicating that CD8+ lymphocytes reduce the average lifespan of productively infected cells during acute infection and early ART, presumably through SIV-specific cytotoxic T lymphocyte (CTL) activity. However, CD8+ depletion did not change the frequency of infected CD4+ T cells in the blood or lymph node as measured by the total cell-associated viral DNA or intact provirus DNA assay. In addition, the size of the persistent reservoir remained the same when measuring the kinetics of virus rebound after ART interruption. These data indicate that during early SIV infection, the viral reservoir that persists under ART is established largely independent of CTL control.