A quantitative approach for measuring the reservoir of latent HIV-1 proviruses.

Autor: Bruner KM; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Molecular Biosciences, University of Texas, Austin, TX, USA., Wang Z; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Simonetti FR; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Bender AM; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Kwon KJ; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Sengupta S; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Fray EJ; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Beg SA; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Antar AAR; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Jenike KM; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Bertagnolli LN; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Capoferri AA; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Kufera JT; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Timmons A; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Nobles C; Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA., Gregg J; Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA., Wada N; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA., Ho YC; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Microbial Pathogenesis, Yale School of Medicine, New Haven, CT, USA., Zhang H; Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA., Margolick JB; Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA., Blankson JN; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Deeks SG; Department of Medicine, University of California San Francisco, San Francisco, CA, USA., Bushman FD; Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA., Siliciano JD; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Laird GM; Accelevir Diagnostics, Baltimore, MD, USA., Siliciano RF; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. rsiliciano@jhmi.edu.; Howard Hughes Medical Institute, Baltimore, MD, USA. rsiliciano@jhmi.edu.
Jazyk: angličtina
Zdroj: Nature [Nature] 2019 Feb; Vol. 566 (7742), pp. 120-125. Date of Electronic Publication: 2019 Jan 30.
DOI: 10.1038/s41586-019-0898-8
Abstrakt: A stable latent reservoir for HIV-1 in resting CD4 + T cells is the principal barrier to a cure 1-3 . Curative strategies that target the reservoir are being tested 4,5 and require accurate, scalable reservoir assays. The reservoir was defined with quantitative viral outgrowth assays for cells that release infectious virus after one round of T cell activation 1 . However, these quantitative outgrowth assays and newer assays for cells that produce viral RNA after activation 6 may underestimate the reservoir size because one round of activation does not induce all proviruses 7 . Many studies rely on simple assays based on polymerase chain reaction to detect proviral DNA regardless of transcriptional status, but the clinical relevance of these assays is unclear, as the vast majority of proviruses are defective 7-9 . Here we describe a more accurate method of measuring the HIV-1 reservoir that separately quantifies intact and defective proviruses. We show that the dynamics of cells that carry intact and defective proviruses are different in vitro and in vivo. These findings have implications for targeting the intact proviruses that are a barrier to curing HIV infection.
Databáze: MEDLINE
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