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Cited by 65HIV Research and TreatmentHIV/AIDS drug development and treatmentInfectious Diseases and Tuberculosis

Characterization of HIV-1 Infection in Microglia-Containing Human Cerebral Organoids

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Gumbs, Stephanie B. H., Berdenis van Berlekom, Amber, Kübler, Raphael, Schipper, Pauline J., Gharu, Lavina, Boks, Marco P., Ormel, Paul R., Wensing, Annemarie M. J. +2 more·2022·Viruses
DOI 10.3390/v14040829PMC PMC9032670
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Abstract

The achievement of an HIV cure is dependent on the eradication or permanent silencing of HIV-latent viral reservoirs, including the understudied central nervous system (CNS) reservoir. This requires a deep understanding of the molecular mechanisms of HIV’s entry into the CNS, latency establishment, persistence, and reversal. Therefore, representative CNS culture models that reflect the intercellular dynamics and pathophysiology of the human brain are urgently needed in order to study the CNS viral reservoir and HIV-induced neuropathogenesis. In this study, we characterized a human cerebral organoid model in which microglia grow intrinsically as a CNS culture model to study HIV infection in the CNS. We demonstrated that both cerebral organoids and isolated organoid-derived microglia (oMG), infected with replication-competent HIVbal reporter viruses, support productive HIV infection via the CCR5 co-receptor. Productive HIV infection was only observed in microglial cells. Fluorescence analysis revealed microglia as the only HIV target cell. Susceptibility to HIV infection was dependent on the co-expression of microglia-specific markers and the CD4 and CCR5 HIV receptors. Altogether, this model will be a valuable tool within the HIV research community to study HIV–CNS interactions, the underlying mechanisms of HIV-associated neurological disorders (HAND), and the efficacy of new therapeutic and curative strategies on the CNS viral reservoir.

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  • CD4 can be upregulated on microglia during a human immunodeficiency virus infection.

    “it is important to note that CD4 can be upregulated on microglia during an human immunodeficiency virus infection 22 and CD8 has been found on microglia/macrophages after a stroke. 23”

    From The MR1/MAIT cell axis enhances dystrophic neurite development in Alzheimer's disease (2025) · cites this paper as [22]

    The Results (§3.1; page unavailable) report CD4 expression on microglia, and the Introduction (§1; page unavailable) describes CD4 as a receptor involved in HIV infection of microglia. Neither passage says that HIV infection upregulates CD4; the cited paper supports its presence, not the claimed increase. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

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Authors
Gumbs, S. B. H., Berdenis van Berlekom, A., Kübler, R., Schipper, P. J., Gharu, L., Boks, M. P., Ormel, P. R., Wensing, A. M. J., de Witte, L. D., & Nijhuis, M.
Affiliations
  • University Medical Center Utrecht (NL)
  • Department of Psychiatry, University Medical Center Utrect Brain Center, Utrecht University, 3584 CG Utrecht, The Netherlands
  • Utrecht University (NL)
Corresponding author
Nijhuis, Monique
ORCID
Venue
Viruses
Publisher
MDPI AG
Published
2022-04-16
Volume
14
Issue
4
Pages
829
ISSN
1999-4915 (ISSN-L)
DOI
10.3390/v14040829
PMC
PMC9032670
OpenAlex
W4224214693
Cited by
65
References
7
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4.37
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journal article
Language
en
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  • Viruses (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
  • Radboud Repository (Radboud University) (submittedVersion)
  • Radboud Repository (Radboud University) (submittedVersion, other-oa)
Funders
  • Aidsfonds (P-13204, P-37203)
  • Health Holland (LSHM2OO12-SGF, LSHM19101-SGF)
  • National Institute of Mental Health (R21MH120581)
Topics
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
  • Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
  • Health Sciences › Medicine › Surgery › Infectious Diseases and Tuberculosis
Keywords
HIV-1 infection, microglia, brain organoids, HIV latency, CCR5 coreceptor, CD4, HIV-associated neurological disease, HIV cure
MeSH terms
Humans, Organoids, HIV-1, HIV Infections, Receptors, HIV, AIDS-Associated Nephropathy, Microglia

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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