Journal
JOURNAL OF CLINICAL INVESTIGATION
Volume 128, Issue 10, Pages 4501-4509Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI121678
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Funding
- NIH [K08 AI 081544, R01 DA 016078, R56 AI 118445, R01 AI024333, R01 OD 011095, R01 AI116868, P01 AI131365]
- amfAR grant [108814-55-RGRL, 108707-54-RKRL]
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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 t(1/2), 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.
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