HIV Controllers Exhibit Effective Cd8+T Cell Recognition of Hiv-1 Infected Non-Activated Cd4+T Cells

Abstract

Even with sustained antiretroviral therapy, resting CD4+ T cells remain a persistent reservoir of HIV infection, representing a critical barrier to HIV cure. Here we demonstrated that CD8+ T cells recognize infected, non-activated CD4+ T cells in the absence of de novo protein production, as measured by immune synapse formation, degranulation, cytokine production and killing of infected cells. Immune recognition was induced by HLA-I presentation of peptides derived from incoming viral particles, and recognition occurred either following cell-free virus infection or following cell-to-cell spread. Importantly, CD8+ T cells from HIV Controllers mediated more effective immune recognition than CD8+ T cells from Progressors. These results indicate that non-activated HIV infected CD4+ T cells can be targeted by CD8+ T cells directly after HIV entry, before reverse transcription and thus before establishment of latency, and suggest a mechanism whereby the immune response may impact the size of the HIV reservoir.