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Human microglial models to study HIV infection and neuropathogenesis: a literature overview and comparative analyses

HIV persistence in the CNS despite antiretroviral therapy may cause neurological disorders and poses a critical challenge for HIV cure. Understanding the pathobiology of HIV-infected microglia, the main viral CNS reservoir, is imperative. Here, we provide a comprehensive comparison of human microgli...

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Autores principales: Gumbs, Stephanie B. H., Kübler, Raphael, Gharu, Lavina, Schipper, Pauline J., Borst, Anne L., Snijders, Gijsje J. L. J., Ormel, Paul R., van Berlekom, Amber Berdenis, Wensing, Annemarie M. J., de Witte, Lot D., Nijhuis, Monique
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9076745/
https://www.ncbi.nlm.nih.gov/pubmed/35138593
http://dx.doi.org/10.1007/s13365-021-01049-w
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author Gumbs, Stephanie B. H.
Kübler, Raphael
Gharu, Lavina
Schipper, Pauline J.
Borst, Anne L.
Snijders, Gijsje J. L. J.
Ormel, Paul R.
van Berlekom, Amber Berdenis
Wensing, Annemarie M. J.
de Witte, Lot D.
Nijhuis, Monique
author_facet Gumbs, Stephanie B. H.
Kübler, Raphael
Gharu, Lavina
Schipper, Pauline J.
Borst, Anne L.
Snijders, Gijsje J. L. J.
Ormel, Paul R.
van Berlekom, Amber Berdenis
Wensing, Annemarie M. J.
de Witte, Lot D.
Nijhuis, Monique
author_sort Gumbs, Stephanie B. H.
collection PubMed
description HIV persistence in the CNS despite antiretroviral therapy may cause neurological disorders and poses a critical challenge for HIV cure. Understanding the pathobiology of HIV-infected microglia, the main viral CNS reservoir, is imperative. Here, we provide a comprehensive comparison of human microglial culture models: cultured primary microglia (pMG), microglial cell lines, monocyte-derived microglia (MDMi), stem cell–derived microglia (iPSC-MG), and microglia grown in 3D cerebral organoids (oMG) as potential model systems to advance HIV research on microglia. Functional characterization revealed phagocytic capabilities and responsiveness to LPS across all models. Microglial transcriptome profiles of uncultured pMG showed the highest similarity to cultured pMG and oMG, followed by iPSC-MG and then MDMi. Direct comparison of HIV infection showed a striking difference, with high levels of viral replication in cultured pMG and MDMi and relatively low levels in oMG resembling HIV infection observed in post-mortem biopsies, while the SV40 and HMC3 cell lines did not support HIV infection. Altogether, based on transcriptional similarities to uncultured pMG and susceptibility to HIV infection, MDMi may serve as a first screening tool, whereas oMG, cultured pMG, and iPSC-MG provide more representative microglial culture models for HIV research. The use of current human microglial cell lines (SV40, HMC3) is not recommended. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13365-021-01049-w.
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spelling pubmed-90767452022-05-08 Human microglial models to study HIV infection and neuropathogenesis: a literature overview and comparative analyses Gumbs, Stephanie B. H. Kübler, Raphael Gharu, Lavina Schipper, Pauline J. Borst, Anne L. Snijders, Gijsje J. L. J. Ormel, Paul R. van Berlekom, Amber Berdenis Wensing, Annemarie M. J. de Witte, Lot D. Nijhuis, Monique J Neurovirol Article HIV persistence in the CNS despite antiretroviral therapy may cause neurological disorders and poses a critical challenge for HIV cure. Understanding the pathobiology of HIV-infected microglia, the main viral CNS reservoir, is imperative. Here, we provide a comprehensive comparison of human microglial culture models: cultured primary microglia (pMG), microglial cell lines, monocyte-derived microglia (MDMi), stem cell–derived microglia (iPSC-MG), and microglia grown in 3D cerebral organoids (oMG) as potential model systems to advance HIV research on microglia. Functional characterization revealed phagocytic capabilities and responsiveness to LPS across all models. Microglial transcriptome profiles of uncultured pMG showed the highest similarity to cultured pMG and oMG, followed by iPSC-MG and then MDMi. Direct comparison of HIV infection showed a striking difference, with high levels of viral replication in cultured pMG and MDMi and relatively low levels in oMG resembling HIV infection observed in post-mortem biopsies, while the SV40 and HMC3 cell lines did not support HIV infection. Altogether, based on transcriptional similarities to uncultured pMG and susceptibility to HIV infection, MDMi may serve as a first screening tool, whereas oMG, cultured pMG, and iPSC-MG provide more representative microglial culture models for HIV research. The use of current human microglial cell lines (SV40, HMC3) is not recommended. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13365-021-01049-w. Springer International Publishing 2022-02-09 2022 /pmc/articles/PMC9076745/ /pubmed/35138593 http://dx.doi.org/10.1007/s13365-021-01049-w Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Gumbs, Stephanie B. H.
Kübler, Raphael
Gharu, Lavina
Schipper, Pauline J.
Borst, Anne L.
Snijders, Gijsje J. L. J.
Ormel, Paul R.
van Berlekom, Amber Berdenis
Wensing, Annemarie M. J.
de Witte, Lot D.
Nijhuis, Monique
Human microglial models to study HIV infection and neuropathogenesis: a literature overview and comparative analyses
title Human microglial models to study HIV infection and neuropathogenesis: a literature overview and comparative analyses
title_full Human microglial models to study HIV infection and neuropathogenesis: a literature overview and comparative analyses
title_fullStr Human microglial models to study HIV infection and neuropathogenesis: a literature overview and comparative analyses
title_full_unstemmed Human microglial models to study HIV infection and neuropathogenesis: a literature overview and comparative analyses
title_short Human microglial models to study HIV infection and neuropathogenesis: a literature overview and comparative analyses
title_sort human microglial models to study hiv infection and neuropathogenesis: a literature overview and comparative analyses
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9076745/
https://www.ncbi.nlm.nih.gov/pubmed/35138593
http://dx.doi.org/10.1007/s13365-021-01049-w
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