CD4+ CD151+ T cells may serve as preferential reservoir cells of latent HIV infection events.

Abstract

Abstract We have demonstrated that the tetraspanin CD151 marks a hyperactivated, pro-inflammatory human CD4+ T cell population. Expansion of this population in HIV patients on ART may explain the associated risk of inflammation-related co-morbidities. However, CD151+ CD4 T cells can also proliferate independent of cognate antigen recognition, driven by just IL-2, a feature that is reminiscent of latently infected T cells which have been reported to maintain the latent reservoir size by homeostatic proliferation mechanisms. The objective of this study was to test our hypothesis that the CD4+CD151+ T cell population is more likely to host latent HIV infection events. First, we noted that all latently HIV-1 infected T cell clones we investigated had upregulated CD151 expression. Using samples from PLWH on ART (n=5) with undetectable viral loads and CD4 count >500 cells/mm3 we enriched CD4+CD151+ and CD4+CD151− T cell populations. Using a nested ALU/GAG qPCR assay to determine the level of proviral HIV-1 integration events, we found a 3.6-fold increase in integration events in the enriched CD4+CD151+ T cell population. Given the demonstrated correlation of proviral DNA frequencies and latent reservoir size, this would suggest that CD151+ T cells disproportionately harbor latent HIV infection, and that CD151+ T cells could be used as a surrogate population to study pertinent features of latently HIV-1 infected T cells. We here begin to address the conundrum of how T cells with a hyperactivated phenotype can host latent HIV-1 infection events and dissect the influence of CD151 expression on latency establishment and reactivation. Characterization of this T cell compartment may reveal new molecular targets to efficiently trigger HIV-1 reactivation. Supported by grants from NIH: NIH R01-AI122842 NIH R33-AI116188 NIH R33-AI133679