CD32⁺CD4⁺ T Cells Are Highly Enriched for HIV DNA and Can Support Transcriptional Latency

The HIV latent reservoir forms the major hurdle to an HIV cure. The discovery of CD32 as marker of this reservoir has aroused much interest, but subsequent reports have challenged this finding. Here, we observe a positive correlation between the percentages of CD32⁺ cells among CD4⁺ T cells of aviremic cART-treated, HIV-infected individuals and their HIV DNA loads in peripheral blood. Moreover, optimization of the CD32⁺CD4⁺ T cell purification protocol reveals prominent enrichment for HIV DNA (mean, 292-fold) in these cells. However, no enrichment for HIV RNA is observed in CD32⁺CD4⁺ cells, yielding significantly reduced HIV RNA/DNA ratios. Furthermore, HIV proviruses in CD32⁺CD4⁺ cells can be reactivated ex vivo to produce virus, strongly suggesting that these cells support HIV transcriptional latency. Our results underscore the importance of isolating pure, bona fide CD32⁺CD4⁺ T cells for future studies and indicate that CD32 remains a promising candidate marker of the HIV reservoir.