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Characterization of HIV-1 Infection in Microglia-Containing Human Cerebral Organoids.
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; de Witte, Lot D; Nijhuis, Monique.
Afiliación
  • Gumbs SBH; Translational Virology, Department of Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
  • Berdenis van Berlekom A; Department of Psychiatry, University Medical Center Utrect Brain Center, Utrecht University, 3584 CG Utrecht, The Netherlands.
  • Kübler R; Department of Translational Neuroscience, University Medical Center Utrecht Brain Center, Utrecht University, 3584 CG Utrecht, The Netherlands.
  • Schipper PJ; Translational Virology, Department of Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
  • Gharu L; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Boks MP; Translational Virology, Department of Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
  • Ormel PR; Translational Virology, Department of Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
  • Wensing AMJ; Department of Psychiatry, University Medical Center Utrect Brain Center, Utrecht University, 3584 CG Utrecht, The Netherlands.
  • de Witte LD; Department of Psychiatry, University Medical Center Utrect Brain Center, Utrecht University, 3584 CG Utrecht, The Netherlands.
  • Nijhuis M; Translational Virology, Department of Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
Viruses ; 14(4)2022 04 16.
Article en En | MEDLINE | ID: mdl-35458559
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones por VIH / Nefropatía Asociada a SIDA / VIH-1 / Microglía Límite: Humans Idioma: En Revista: Viruses Año: 2022 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Suiza
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones por VIH / Nefropatía Asociada a SIDA / VIH-1 / Microglía Límite: Humans Idioma: En Revista: Viruses Año: 2022 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Suiza