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 in | Journal of neuroimmune pharmacology Vol. 14; no. 1; pp. 110 - 119 |
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| Main Authors | , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
New York
Springer US
01.03.2019
Springer Nature B.V |
| Subjects | |
| Online Access | Get full text |
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| 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. |
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| AbstractList | 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. |
| Author | Ko, Allen Kim, Woong-Ki Zhang, Junfeng Kang, Guobin Hattler, Julian B. Galadima, Hadiza I. Li, Qingsheng |
| Author_xml | – sequence: 1 givenname: Allen surname: Ko fullname: Ko, Allen organization: Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School – sequence: 2 givenname: Guobin surname: Kang fullname: Kang, Guobin organization: Nebraska Center for Virology, School of Biological Sciences, University of Nebraska-Lincoln – sequence: 3 givenname: Julian B. surname: Hattler fullname: Hattler, Julian B. organization: Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School – sequence: 4 givenname: Hadiza I. surname: Galadima fullname: Galadima, Hadiza I. organization: Graduate Program in Public Health, Eastern Virginia Medical School, School of Community and Environmental Health, College of Health Sciences, Old Dominion University – sequence: 5 givenname: Junfeng surname: Zhang fullname: Zhang, Junfeng organization: Nebraska Center for Virology, School of Biological Sciences, University of Nebraska-Lincoln, Department of Human Anatomy, Xi’an Medical University – sequence: 6 givenname: Qingsheng surname: Li fullname: Li, Qingsheng email: qli@unl.edu organization: Nebraska Center for Virology, School of Biological Sciences, University of Nebraska-Lincoln – sequence: 7 givenname: Woong-Ki surname: Kim fullname: Kim, Woong-Ki email: kimw@evms.edu organization: Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/30194646$$D View this record in MEDLINE/PubMed |
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| Copyright | The Author(s) 2018. corrected publication November/2018 Journal of Neuroimmune Pharmacology is a copyright of Springer, (2018). All Rights Reserved. © 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. The Author(s) 2018, corrected publication November/2018 |
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| Keywords | HIV-1 Brain Reservoir Antiretroviral therapy HIV-associated neurocognitive disorders Macrophage |
| Language | English |
| License | Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
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| SubjectTerms | Antiretroviral drugs Biomedical and Life Sciences Biomedicine Brain Cell Biology Deoxyribonucleic acid DNA Drug therapy Immunology Neurosciences Original Original Article Pharmacology/Toxicology Virology |
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| Title | Macrophages but not Astrocytes Harbor HIV DNA in the Brains of HIV-1-Infected Aviremic Individuals on Suppressive Antiretroviral Therapy |
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