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

• Published in: Cell reports (Cambridge) 2020-02, Vol.30 (7), p.2284-2296.e3
• Main Authors: Darcis, Gilles, Kootstra, Neeltje A., Hooibrink, Berend, van Montfort, Thijs, Maurer, Irma, Groen, Kevin, Jurriaans, Suzanne, Bakker, Margreet, van Lint, Carine, Berkhout, Ben, Pasternak, Alexander O.
• Format: Article
• Language: English
• Subjects: antiretroviral therapy; biomarker; CD32; CD32 antigen; CD4+ T lymphocyte; CD4-Positive T-Lymphocytes - metabolism; DNA transcription; DNA, Viral - genetics; HIV cure; HIV latency; HIV persistence; HIV reservoir; HIV-1 - genetics; Human health sciences; Human immunodeficiency virus infection; Humans; Immunologie & maladie infectieuse; Immunology & infectious disease; Receptors, IgG - metabolism; Sciences de la santé humaine; Virus Latency - genetics
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2020.01.071

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. [Display omitted] •Percentages of CD32+ cells among CD4+ T cells correlate with HIV DNA loads in PBMC•High enrichment for HIV DNA in purified CD32+CD4+ cells from cART-treated patients•HIV transcription level per provirus is reduced in patient-derived CD32+CD4+ cells•HIV proviruses in purified CD32+CD4+ cells can be reactivated ex vivo to produce virus CD32a was recently proposed to mark the HIV reservoir, but this finding was subsequently challenged. By using a sequential cell-sorting protocol to purify bona fide CD32+CD4+ cells, Darcis et al. demonstrate HIV DNA enrichment and ex vivo reactivation-mediated virus production in these cells, reinforcing CD32 as an HIV reservoir marker.