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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Bibliographic Details
Published in:Journal of neurovirology 2022-02, Vol.28 (1), p.64-91
Main Authors: 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
Format: Article
Language:English
Subjects:
Biomedical and Life Sciences
Biomedicine
Cells, Cultured
HIV Infections - pathology
HIV-1 - genetics
Humans
Immunology
Infectious Diseases
Microglia - pathology
Monocytes
Neurology
Neurosciences
Virology
Virus Replication
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Summary: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.
ISSN:1355-0284
1538-2443
DOI:10.1007/s13365-021-01049-w