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No recovery of replication-competent HIV-1 from human liver macrophages
Abraham J. Kandathil, … , Alan S. Perelson, Ashwin Balagopal
Abraham J. Kandathil, … , Alan S. Perelson, Ashwin Balagopal
Published September 10, 2018
Citation Information: J Clin Invest. 2018;128(10):4501-4509. https://doi.org/10.1172/JCI121678.
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Research Article AIDS/HIV Infectious disease

No recovery of replication-competent HIV-1 from human liver macrophages

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Abstract

Long-lived HIV-1 reservoirs that persist despite antiretroviral therapy (ART) are a major impediment to a cure for HIV-1. We examined whether human liver macrophages (LMs), the largest tissue macrophage population, comprise an HIV-1 reservoir. We purified LMs from liver explants and included treatment with a T cell immunotoxin to reduce T cells to 1% or less. LMs were purified from 9 HIV-1–infected persons, 8 of whom were on ART (range 8–140 months). Purified LMs were stimulated ex vivo and supernatants from 6 of 8 LMs from persons on ART transmitted infection. However, HIV-1 propagation from LMs was not sustained except in LMs from 1 person taking ART for less than 1 year. Bulk liver sequences matched LM-derived HIV-1 in 5 individuals. Additional in vitro experiments undertaken to quantify the decay of HIV-1–infected LMs from 3 healthy controls showed evidence of infection and viral release for prolonged durations (>170 days). Released HIV-1 propagated robustly in target cells, demonstrating that viral outgrowth was observable using our methods. The t1/2 of HIV-1–infected LMs ranged from 3.8–55 days. These findings suggest that while HIV-1 persists in LMs during ART, it does so in forms that are inert, suggesting that they are defective or restricted with regard to propagation.

Authors

Abraham J. Kandathil, Sho Sugawara, Ashish Goyal, Christine M. Durand, Jeffrey Quinn, Jaiprasath Sachithanandham, Andrew M. Cameron, Justin R. Bailey, Alan S. Perelson, Ashwin Balagopal

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Figure 2

Schema for VOA performed on purified LMs.

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Schema for VOA performed on purified LMs.
After purification of primary ...
After purification of primary human LMs from HIV-1–infected subjects, cells were maintained ex vivo for more than 30 days. The VOA was performed on LMs from individuals taking ART. Isolated LMs were treated with Resimmune over 48 hours to deplete any remaining T cells. Following stimulation with IFNG and HIV-1 rTat, LM supernatants were filtered and transferred to target cells twice over 15 days and incubated. In addition, target cells were added to LMs. Cell-associated and supernatant HIV-1 DNA and RNA levels were measured on day 11 in target cells.
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