Naive CD4+ T Cells Harbor a Large Inducible Reservoir of Latent, Replication-competent Human Immunodeficiency Virus Type 1. (7th February 2019)

• Record Type: Journal Article
• Authors: Zerbato, Jennifer M; McMahon, Deborah K; Sobolewski, Michelle D; Mellors, John W; Sluis-Cremer, Nicolas
• Is Part Of: Clinical infectious diseases. Volume 69:Number 11(2019)
• Page Start: 1919
• Page End: 1925
• Publication Date: 2019-02-07
• Subjects: HIV-1 -- latent -- reservoir -- naive -- memory; Communicable diseases -- Periodicals; 616.905
• DOI: 10.1093/cid/ciz108
• Languages: English
• ISSNs: 1058-4838

Abstract

Abstract: Background: The latent human immunodeficiency virus type 1 (HIV-1) reservoir represents a major barrier to a cure. Based on the levels of HIV-1 DNA in naive (TN ) vs resting memory CD4+ T cells, it is widely hypothesized that this reservoir resides primarily within memory cells. Here, we compared virus production from TN and central memory (TCM ) CD4+ T cells isolated from HIV-1–infected individuals on suppressive therapy. Methods: CD4+ TN and TCM cells were purified from the blood of 7 HIV-1–infected individuals. We quantified total HIV-1 DNA in the CD4+ TN and TCM cells. Extracellular virion-associated HIV-1 RNA or viral outgrowth assays were used to assess latency reversal following treatment with anti-CD3/CD28 monoclonal antibodies (mAbs), phytohaemagglutinin/interleukin-2, phorbol 12-myristate 13-acetate/ionomycin, prostratin, panobinostat, or romidepsin. Results: HIV-1 DNA was significantly higher in TCM compared to TN cells (2179 vs 684 copies/10 6 cells, respectively). Following exposure to anti-CD3/CD28 mAbs, virion-associated HIV-1 RNA levels were similar between TCM and TN cells (15 135 vs 18 290 copies/mL, respectively). In 4/7 donors, virus production was higher for TN cells independent of the latency reversing agent used. Replication-competent virus was recovered from both TN and TCM cells. Conclusions: Although the frequency of HIV-1 infection is lower in TN compared to TCM cells, as much virus is produced from the TN population after latency reversal. This finding suggests that quantifying HIV-1 DNA alone may not predict the size of the inducible latent reservoir and that TN cells may be an important reservoir of latent HIV-1. Abstract : In this study, we show that although the frequency of human immunodeficiency virus type 1 infection is lower in naïve compared to central memory cells CD4+ T cells, as much virus is produced from the naive population following latency reversal.