Abstract
SUMMARYThe 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.
Highlights
Combination antiretroviral therapy allows clinicians to successfully manage most HIV-infected individuals, to prevent the development of AIDS, and to considerably reduce the risk of virus transmission
The source of the viral rebound after therapy is stopped is the latent HIV reservoir, which is considered the major hurdle to an HIV cure
We demonstrated that by further purification of the CD32+CD4+ cells, one can move from no enrichment to prominent enrichment for HIV DNA, but not for CA HIV RNA, in these cells
Summary
Combination antiretroviral therapy (cART) allows clinicians to successfully manage most HIV-infected individuals, to prevent the development of AIDS, and to considerably reduce the risk of virus transmission. The source of the viral rebound after therapy is stopped is the latent HIV reservoir, which is considered the major hurdle to an HIV cure. The definition of the viral reservoir could be extended to all infected cells, including those infected with defective proviruses (Avettand-Fenoel et al, 2016). HIV can persist during cART in central, transitional, and effector memory CD4+ T cells, in addition to naive CD4+ T cells (Chomont et al, 2009; Khoury et al, 2016; Wightman et al, 2010). CD4+ T memory stem cells stand out as another cell population in which long-term HIV persistence is evident, likely because of their superior ability for self-renewal, resistance to apoptosis, and extended lifespan (Buzon et al, 2014; Gattinoni et al, 2011). Lymph node follicular helper T cells, as well as their blood-circulating counterpart, represent yet another cellular location for persisting virus during cART (Banga et al, 2016, 2018)
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