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

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 t...

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Published inJournal of neuroimmune pharmacology Vol. 14; no. 1; pp. 110 - 119
Main Authors Ko, Allen, Kang, Guobin, Hattler, Julian B., Galadima, Hadiza I., Zhang, Junfeng, Li, Qingsheng, Kim, Woong-Ki
Format Journal Article
LanguageEnglish
Published New York Springer US 01.03.2019
Springer Nature B.V
Subjects
Antiretroviral drugs
Biomedical and Life Sciences
Biomedicine
Brain
Cell Biology
Deoxyribonucleic acid
DNA
Drug therapy
Immunology
Neurosciences
Original
Original Article
Pharmacology/Toxicology
Virology
HIV-1
Brain
Reservoir
Antiretroviral therapy
HIV-associated neurocognitive disorders
Macrophage
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Summary: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.
ISSN:1557-1890
1557-1904
DOI:10.1007/s11481-018-9809-2