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
(2022) Journal of Neurovirology, volume 28, issue 1, pp. 64 - 91
(Article)
Abstract
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
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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.
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Keywords: Central nervous system, HIV, HIV-associated neurocognitive disorder, Microglia, Neuropathogenesis, Organoid, Humans, Cells, Cultured, Microglia/pathology, Monocytes, Virus Replication, HIV-1/genetics, HIV Infections/pathology, Clinical Neurology, Neurology, Cellular and Molecular Neuroscience, Virology, Review, Research Support, Non-U.S. Gov't, Journal Article, Research Support, N.I.H., Extramural
ISSN: 1355-0284
Publisher: Springer New York
Note: Funding Information: This work was financially supported by grants from the Aidsfonds (P‐13204; P‐37203, Health Holland (LSHM2OO12‐SGF) and NIHM (R21MH120581). The authors thank the team of the Netherlands Brain Bank ( http://www.brainbank.nl ) for their services. We thank the study participants for their generous gift of brain donation. We are grateful to The MIND Facility and Daniëlle Vonk, who helped with fibroblasts and iPSC culture and characterization, and to F.A.J. Gigase for teaching and advice on organoid differentiation and culture. Funding Information: This work was financially supported by grants from the Aidsfonds (P‐13204; P‐37203, Health Holland (LSHM2OO12‐SGF) and NIHM (R21MH120581). The authors thank the team of the Netherlands Brain Bank (http://www.brainbank.nl) for their services. We thank the study participants for their generous gift of brain donation. We are grateful to The MIND Facility and Daniëlle Vonk, who helped with fibroblasts and iPSC culture and characterization, and to F.A.J. Gigase for teaching and advice on organoid differentiation and culture. Publisher Copyright: © 2022, The Author(s). © 2022. The Author(s).
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