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J Neuroimmune Pharmacol. 2018 Sep 7. doi: 10.1007/s11481-018-9809-2. [Epub ahead of print]

Macrophages but not Astrocytes Harbor HIV DNA in the Brains of HIV-1-Infected Aviremic Individuals on Suppressive Antiretroviral Therapy.

Author information

1
Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA, USA.
2
Nebraska Center for Virology, School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE, USA.
3
Graduate Program in Public Health, Eastern Virginia Medical School, Norfolk, VA, USA.
4
School of Community and Environmental Health, College of Health Sciences, Old Dominion University, Norfolk, VA, USA.
5
Department of Human Anatomy, Xi'an Medical University, Shaanxi, China.
6
Nebraska Center for Virology, School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE, USA. qli@unl.edu.
7
Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA, USA. kimw@evms.edu.

Abstract

The question of whether the human brain is an anatomical site of persistent HIV-1 infection during suppressive antiretroviral therapy (ART) is critical, but remains unanswered. The presence of virus in the brains of HIV patients whose viral load is effectively suppressed would demonstrate not only the potential for CNS to act as an anatomical HIV reservoir, but also the urgent need to understand the factors contributing to persistent HIV behind the blood-brain barrier. Here, we investigated for the first time the presence of cells harboring HIV DNA and RNA in the brains from subjects with undetectable plasma viral load and sustained viral suppression, as identified by the National NeuroAIDS Tissue Consortium. Using new, highly sensitive in situ hybridization techniques, RNAscope and DNAscope, in combination with immunohistochemistry, we were able to detect HIV-1 in the brains of all virally suppressed cases and found that brain macrophages and microglia, but not astrocytes, were the cells harboring HIV DNA in the brain. This study demonstrated that HIV reservoirs persist in brain macrophages/microglia during suppressive ART, which cure/treatment strategies will need to focus on targeting.

KEYWORDS:

Antiretroviral therapy; Brain; HIV-1; HIV-associated neurocognitive disorders; Macrophage; Reservoir

PMID:
30194646
DOI:
10.1007/s11481-018-9809-2

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