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Nature. 2019 Feb;566(7742):120-125. doi: 10.1038/s41586-019-0898-8. Epub 2019 Jan 30.

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

Author information

1
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
2
Department of Molecular Biosciences, University of Texas, Austin, TX, USA.
3
Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
4
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
5
Department of Microbial Pathogenesis, Yale School of Medicine, New Haven, CT, USA.
6
Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
7
Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
8
Accelevir Diagnostics, Baltimore, MD, USA.
9
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. rsiliciano@jhmi.edu.
10
Howard Hughes Medical Institute, Baltimore, MD, USA. rsiliciano@jhmi.edu.

Abstract

A stable latent reservoir for HIV-1 in resting CD4+ T cells is the principal barrier to a cure1-3. Curative strategies that target the reservoir are being tested4,5 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 activation1. However, these quantitative outgrowth assays and newer assays for cells that produce viral RNA after activation6 may underestimate the reservoir size because one round of activation does not induce all proviruses7. 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 defective7-9. 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.

PMID:
30700913
DOI:
10.1038/s41586-019-0898-8

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