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

Autor: Gumbs SBH; Translational Virology, Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands., Kübler R; Translational Virology, Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.; Department of Psychiatry, Icahn School of Medicine, New York, NY, USA., Gharu L; Translational Virology, Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands., Schipper PJ; Translational Virology, Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands., Borst AL; Translational Virology, Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands., Snijders GJLJ; Department of Psychiatry, Icahn School of Medicine, New York, NY, USA.; Department of Psychiatry, University Medical Center Utrecht, Brain Center, Utrecht University, Utrecht, The Netherlands., Ormel PR; Department of Psychiatry, University Medical Center Utrecht, Brain Center, Utrecht University, Utrecht, The Netherlands., van Berlekom AB; Department of Psychiatry, University Medical Center Utrecht, Brain Center, Utrecht University, Utrecht, The Netherlands.; Department of Translational Neuroscience, University Medical Center Utrecht, Brain Center, Utrecht University, Utrecht, The Netherlands., Wensing AMJ; Translational Virology, Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands., de Witte LD; Department of Psychiatry, Icahn School of Medicine, New York, NY, USA.; Department of Psychiatry, University Medical Center Utrecht, Brain Center, Utrecht University, Utrecht, The Netherlands., Nijhuis M; Translational Virology, Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands. m.nijhuis@umcutrecht.nl.
Jazyk: angličtina
Zdroj: Journal of neurovirology [J Neurovirol] 2022 Feb; Vol. 28 (1), pp. 64-91. Date of Electronic Publication: 2022 Feb 09.
DOI: 10.1007/s13365-021-01049-w
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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