ArticleAIDS (London, England)2020
Productive HIV infection in astrocytes can be established via a nonclassical mechanism.
Article in AIDS (London, England), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 50 citations in OpenAlex.
- HAND in Africa: prevalence, diagnostic challenges and the search for objective markers.Journal of neurovirology · 2026Review
- HIV-1 Tat-driven Glutamate Dysregulation: Implications for Cognitive Impairment in HAND.Current HIV/AIDS reports · 2026Review
- Latent HIV Reservoirs in the Central Nervous System: Mechanisms, Barriers, and Therapeutic Approaches.ACS infectious diseases · 2026Review
- Molecular Regulation of HIV-1 Expression and Persistence Across Diverse Cellular Reservoirs.International journal of molecular sciences · 2026Review
- Sigma-1 receptor regulates HIV-1 and methamphetamine-induced endothelial/pericyte barrier impairment via strain-specific inflammatory responses and mitochondrial dysregulation.Journal of neuroinflammation · 2026Article
- Lysosome-escaping and nucleus-targeting nanomedicine for enhanced cancer catalytic internal radiotherapy.European journal of nuclear medicine and molecular imaging · 2025Article
- Expression of HIV envelope protein in the human central nervous system.AIDS (London, England) · 2025Article
- Neurotropic Viruses as Acute and Insidious Drivers of Aging.Biomolecules · 2025Review
- The challenges to detect, quantify, and characterize viral reservoirs in the current antiretroviral era.NeuroImmune pharmacology and therapeutics · 2024Review
- Review
- HIV-1 infection of genetically engineered iPSC-derived central nervous system-engrafted microglia in a humanized mouse model.Journal of virology · 2023Article
- Human iPSC-derived brain organoids: A 3D mini-brain model for studying HIV infection.Experimental neurology · 2023Article
- Progressive Degeneration and Adaptive Excitability in Dopamine D1 and D2 Receptor-Expressing Striatal Neurons Exposed to HIV-1 Tat and Morphine.Cellular and molecular neurobiology · 2023Article
- Biotypes of Central Nervous System Complications in People With Human Immunodeficiency Virus: Virology, Immunology, and Neuropathology.The Journal of infectious diseases · 2023Article
- HIV infection of non-classical cells in the brain.Retrovirology · 2023Review
- Astrocytes: Role in pathogenesis and effect of commonly misused drugs in the HIV infected brain.Current research in neurobiology · 2023Review
- Dopamine, Immunity, and Disease.Pharmacological reviews · 2023Review
- Neuropathogenesis of HIV-1: insights from across the spectrum of acute through long-term treated infection.Seminars in immunopathology · 2022Review
- Directing HIV-1 for degradation by non-target cells, using bi-specific single-chain llama antibodies.Scientific reports · 2022Article
- SUMOylation and Viral Infections of the Brain.Pathogens (Basel, Switzerland) · 2022Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
objectiveAstrocytes are proposed to be a critical reservoir of HIV in the brain. However, HIV infection of astrocytes is inefficient in vitro except for cell-to-cell transmission from HIV-infected cells. Here, we explore mechanisms by which cell-free HIV bypasses entry and postentry barriers leading to a productive infection.
methodsHIV infection of astrocytes was investigated by a variety of techniques including transfection of CD4-expressing plasmid, treatment with lysosomotropic agents or using a transwell culture system loaded with HIV-infected lymphocytes. Infection was monitored by HIV-1 p24 in culture supernatants and integrated proviral DNA was quantified by Alu-PCR.
resultsPersistent HIV infection could be established in astrocytes by transfection of proviral DNA, transduction with VSV-G-pseudotyped viruses, transient expression of CD4 followed by HIV infection, or simultaneous treatment with lysosomotropic chloroquine or Tat-HA2 peptide with HIV infection. In absence of these treatments, HIV entered via endocytosis as seen by electronmicroscopy and underwent lysosomal degradation without proviral integration, indicating endocytosis is a dead end for HIV in astrocytes. Nevertheless, productive infection was observed when astrocytes were in close proximity but physically separated from HIV-infected lymphocytes in the transwell cultures. This occurred with X4 or dual tropic R5X4 viruses and was blocked by an antibody or antagonist to CXCR4.
conclusionA CD4-independent, CXCR4-dependent mechanism of viral entry is proposed, by which immature HIV particles from infected lymphocytes might directly bind to CXCR4 on astrocytes and trigger virus--cell fusion during or after the process of viral maturation. This mechanism may contribute to the formation of brain HIV reservoirs.
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