[HTML][HTML] Genetic evidence that naive T cells can contribute significantly to the human immunodeficiency virus intact reservoir: time to re-evaluate their role

EV Rullo, LM Cannon, MR Pinzone… - … Diseases: An Official …, 2019 - ncbi.nlm.nih.gov
EV Rullo, LM Cannon, MR Pinzone, M Ceccarelli, G Nunnari, U O'Doherty
Clinical Infectious Diseases: An Official Publication of the …, 2019ncbi.nlm.nih.gov
To the Editor—We read with interest the article by Zerbato et al [1] on the human
immunodeficiency virus (HIV) reservoir harbored in naive CD4+ T cells (TN cells). We would
like to share our genetic evidence that TN cells harbor a substantial fraction of the intact
reservoir to reinforce the message that TN cells may play a central role in shaping the
reservoir in comparison with central memory CD4+ T cells (TCM cells). We sorted TN cells
(defined as CD45RA+, CCR7+, CD27+) and TCM cells (defined as CD45RA−, CCR7+ …
To the Editor—We read with interest the article by Zerbato et al [1] on the human immunodeficiency virus (HIV) reservoir harbored in naive CD4+ T cells (TN cells). We would like to share our genetic evidence that TN cells harbor a substantial fraction of the intact reservoir to reinforce the message that TN cells may play a central role in shaping the reservoir in comparison with central memory CD4+ T cells (TCM cells). We sorted TN cells (defined as CD45RA+, CCR7+, CD27+) and TCM cells (defined as CD45RA−, CCR7+, CD27+) from CD3+CD8− peripheral blood mononuclear cells of 2 chronically HIV-1–infected donors who were virally suppressed on antiretroviral therapy (ART) for 2 years. We measured total HIV DNA and amplified HIV proviruses at limiting dilution in each subset. We sequenced a total of 365 and 227 near-full-length proviruses in subjects 1 and 2, respectively, as described [2]. All proviruses with an intact envelope (n= 159) in subject 1 were CCR5-tropic while the majority of evaluable proviruses (n= 106) in subject 2 were CXCR4-tropic. Consistent with Zerbato et al [1] and previous reports [3–5], total HIV DNA was higher in TCM cells (4583 and 3717 HIV/million cells for subjects 1 and 2) than in TN cells (654 and 1236, respectively). After proviral sequencing of sorted subsets, we calculated the contribution of intact proviruses/million CD4+ cells by these 2 subsets. Even though the HIV DNA levels were higher in TCM cells for both subjects, the contribution of intact proviruses by TN cells was far greater than by TCM cells, representing 38.5% and 58.7% of the intact reservoir (Figure 1A). Similarly, the percentages of intact proviruses were also higher in TN cells than in TCM cells (Figure 1B).
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