TY - JOUR
T1 - No recovery of replication-competent HIV-1 from human liver macrophages
AU - Kandathil, Abraham J.
AU - Sugawara, Sho
AU - Goyal, Ashish
AU - Durand, Christine M.
AU - Quinn, Jeffrey
AU - Sachithanandham, Jaiprasath
AU - Cameron, Andrew M.
AU - Bailey, Justin R.
AU - Perelson, Alan S.
AU - Balagopal, Ashwin
N1 - Publisher Copyright:
© 2018 American Society for Clinical Investigation. All rights reserved.
PY - 2018/10/1
Y1 - 2018/10/1
N2 - 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.
AB - 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.
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U2 - 10.1172/JCI121678
DO - 10.1172/JCI121678
M3 - Article
C2 - 30198905
AN - SCOPUS:85054433273
SN - 0021-9738
VL - 128
SP - 4501
EP - 4509
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 10
ER -