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

Katherine M. Bruner, Zheng Wang, Francesco R. Simonetti, Alexandra M. Bender, Kyungyoon J. Kwon, Srona Sengupta, Emily J. Fray, Subul A. Beg, Annukka A. R. Antar, Katharine M. Jenike, Lynn N. Bertagnolli, Adam A. Capoferri, Joshua T. Kufera, Andrew Timmons, Christopher Nobles, John Gregg, Nikolas Wada, Ya-Chi Ho, Hao Zhang, Joseph B. Margolick, Joel N. Blankson, Steven G. Deeks, Frederic D. Bushman, Janet D. Siliciano, Gregory M. Laird and Robert F. Siliciano ()
Additional contact information
Katherine M. Bruner: Johns Hopkins University School of Medicine
Zheng Wang: Johns Hopkins University School of Medicine
Francesco R. Simonetti: Johns Hopkins University School of Medicine
Alexandra M. Bender: Johns Hopkins University School of Medicine
Kyungyoon J. Kwon: Johns Hopkins University School of Medicine
Srona Sengupta: Johns Hopkins University School of Medicine
Emily J. Fray: Johns Hopkins University School of Medicine
Subul A. Beg: Johns Hopkins University School of Medicine
Annukka A. R. Antar: Johns Hopkins University School of Medicine
Katharine M. Jenike: Johns Hopkins University School of Medicine
Lynn N. Bertagnolli: Johns Hopkins University School of Medicine
Adam A. Capoferri: Johns Hopkins University School of Medicine
Joshua T. Kufera: Johns Hopkins University School of Medicine
Andrew Timmons: Johns Hopkins University School of Medicine
Christopher Nobles: University of Pennsylvania Perelman School of Medicine
John Gregg: University of Pennsylvania Perelman School of Medicine
Nikolas Wada: Johns Hopkins Bloomberg School of Public Health
Ya-Chi Ho: Johns Hopkins University School of Medicine
Hao Zhang: Johns Hopkins Bloomberg School of Public Health
Joseph B. Margolick: Johns Hopkins Bloomberg School of Public Health
Joel N. Blankson: Johns Hopkins University School of Medicine
Steven G. Deeks: University of California San Francisco
Frederic D. Bushman: University of Pennsylvania Perelman School of Medicine
Janet D. Siliciano: Johns Hopkins University School of Medicine
Gregory M. Laird: Accelevir Diagnostics
Robert F. Siliciano: Johns Hopkins University School of Medicine

Nature, 2019, vol. 566, issue 7742, 120-125

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41586-019-0898-8

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