ArticleMolecular neurodegeneration2019
Human Interleukin-34 facilitates microglia-like cell differentiation and persistent HIV-1 infection in humanized mice.
Article in Molecular neurodegeneration, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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52 citing papers in PubMed, 73 citations in OpenAlex.
- Increased Amyloidogenic Neuronal Injury in HIV-1-infected APP-KI Alzheimer's disease mice.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Humanized immune system animal models and their recent applications.Animal models and experimental medicine · 2026Review
- Exploring the immune environment of glioblastoma in humanized mouse models.Neuro-oncology · 2026Article
- Advancement of humanized mice and leading applications in immunological disease models.Inflammation and regeneration · 2026Review
- Microglia-associated progression of multiple sclerosis: target identification and therapeutic engagement in human in vitro models.Experimental & molecular medicine · 2026Review
- Chimeric brain models to study human glial-neuronal and macroglial-microglial interactions.Cell reports · 2026Article
- The promise and perils of humanized mice: workshop report from the 29th scientific conference of the society on NeuroImmune pharmacology (SNIP).NeuroImmune pharmacology and therapeutics · 2025Article
- Derivation of resident macrophages and construction of tumor microenvironment in Flk-1-knockout chimeric mice produced via blastocyst complementation.Scientific reports · 2025Article
- HIV-1 cell-to-cell infection of macrophages escapes type I interferon and host restriction factors, and is resistant to antiretroviral drugs.PLoS pathogens · 2025Article
- Amyloid precursor protein and presenilin-1 knock-in immunodeficient mice exhibit intraneuronal Aβ pathology, microgliosis, and extensive neuronal loss.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- HIV-1 infection facilitates Alzheimer's disease pathology in humanized APP knock-in immunodeficient mice.NeuroImmune pharmacology and therapeutics · 2025Article
- Human-Mouse Chimeric Brain Models to Study Human Glial-Neuronal and Macroglial-Microglial Interactions.bioRxiv : the preprint server for biology · 2024Article
- In situ analysis of neuronal injury and neuroinflammation during HIV-1 infection.Retrovirology · 2024Article
- Engraftment of adult hematopoietic stem and progenitor cells in a novel model of humanized mice.iScience · 2024Article
- Optimal therapy for HIV infection containment and virions inhibition.Infectious Disease Modelling · 2024Article
- Review
- HIV-1 infection of genetically engineered iPSC-derived central nervous system-engrafted microglia in a humanized mouse model.Journal of virology · 2023Article
- Advancing the preclinical study of comorbid neuroHIV and substance use disorders: Current perspectives and future directions.Brain, behavior, and immunity · 2023Review
- Humanized Mice for Studies of HIV-1 Persistence and Elimination.Pathogens (Basel, Switzerland) · 2023Review
- Human microglial models to study host-virus interactions.Experimental neurology · 2023Review
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundMicroglia are the principal innate immune defense cells of the centeral nervous system (CNS) and the target of the human immunodeficiency virus type one (HIV-1). A complete understanding of human microglial biology and function requires the cell's presence in a brain microenvironment. Lack of relevant animal models thus far has also precluded studies of HIV-1 infection. Productive viral infection in brain occurs only in human myeloid linage microglia and perivascular macrophages and requires cells present throughout the brain. Once infected, however, microglia become immune competent serving as sources of cellular neurotoxic factors leading to disrupted brain homeostasis and neurodegeneration.
methodsHerein, we created a humanized bone-marrow chimera producing human "microglia like" cells in NOD.Cg-Prkdc
resultsHuman interleukin-34 under the control of the cytomegalovirus promoter inserted in NSG mouse strain drove brain reconstitution of HSPC derived peripheral macrophages into microglial-like cells. These human cells expressed canonical human microglial cell markers that included CD14, CD68, CD163, CD11b, ITGB2, CX3CR1, CSFR1, TREM2 and P2RY12. Prior restriction to HIV-1 infection in the rodent brain rested on an inability to reconstitute human microglia. Thus, the natural emergence of these cells from ingressed peripheral macrophages to the brain could allow, for the first time, the study of a CNS viral reservoir. To this end we monitored HIV-1 infection in a rodent brain. Viral RNA and HIV-1p24 antigens were readily observed in infected brain tissues. Deep RNA sequencing of these infected mice and differential expression analysis revealed human-specific molecular signatures representative of antiviral and neuroinflammatory responses.
conclusionsThis humanized microglia mouse reflected human HIV-1 infection in its known principal reservoir and showed the development of disease-specific innate immune inflammatory and neurotoxic responses mirroring what can occur in an infected human brain.
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