Cognate Antigen Engagement Induces HIV-1 Expression In CD4+ T Cells From People On Long-Term ART
Moskovjlevic, M.; Dragoni, F.; Board, N. L.; Wu, F.; Lai, J.; Zhang, H.; White, J. R.; Ho, R.; Lynn, K.; Tebas, P.; Mounzer, K.; Deeks, S. G.; Montaner, L. J.; Siliciano, J. D.; Simonetti, F. R.; Siliciano, R. F.
Show abstract
Despite antiretroviral therapy (ART), HIV-1 persists in latently-infected CD4+ T cells, preventing cure. Antigens drive the proliferation of infected cells, precluding latent reservoir decay. However, the relationship between antigen recognition and HIV-1 gene expression is poorly understood since most studies of latency reversal use agents that induce non-specific global T cell activation. Here, we isolated rare CD4+ T cells responding to cytomegalovirus (CMV) or HIV-1 Gag antigens from participants on long-term ART and assessed T cell activation and HIV-1 RNA expression upon co-culture with autologous dendritic cells (DCs) presenting cognate antigens. Physiological presentation of cognate antigens induced broad T cell activation (median 42-fold increase in CD154+CD69+ cells) and significantly increased HIV-1 transcription (median 4-fold), mostly through the induction of rare cells with higher viral expression. Thus, despite low proviral inducibility, physiologic antigen recognition can promote HIV-1 expression, potentially contributing to spontaneous reservoir activity on ART and viral rebound upon ART interruption.
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