Current research on the levels of HIV-1 DNA in naïve (TN) versus resting memory CD4+ T cells suggests that the latent reservoir is residing primarily within memory cells. The authors were interested in virus production from TN and central memory (TCM) CD4+ T cells isolated from HIV-infected patients suppressed on antiretroviral therapy. They purified the CD4+ TN and TCM cells from the blood of seven HIV-infected patients who had been suppressed for ≥5 years. Total HIV DNA was measured, and extracellular virion-associated HIV RNA or viral outgrowth assays were used to assess latency reversal following treatment with anti-CD3/CD28 mAbs, phytohaemagglutinin/interleukin-2, phorbol 12-myristate 13-acetate/ionomycin, prostratin, panobinostat or romidepsin. The authors found that HIV DNA levels were significantly higher in TCM compared with TN cells (2179 vs. 684 copies/10^6 cells). Following exposure to anti-CD3/CD28 mAbs, virion-associated HIV RNA levels were similar between the two types of cells (15,135 vs. 18,290 copies/mL). In four of the seven donors, virus production was found to be higher for TN cells independent of the latency reversing agent used. Replication-competent virus was recovered from both TN and TCM cells. Therefore, while the frequency of HIV-1 infection is lower in TN compared with TCM cells; as much, if not more, virus is produced from the TN population following exposure to latency reversing agents. This suggests that quantifying HIV DNA levels alone may not predict the entire size of the inducible latent reservoir, with TN cells being a potential important reservoir of latent HIV.
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