ArticleJournal of neurochemistry2013
Cytochrome C dysregulation induced by HIV infection of astrocytes results in bystander apoptosis of uninfected astrocytes by an IP3 and calcium-dependent mechanism.
Article in Journal of neurochemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Implications and prospects of immunological and neuroimaging research in HIV-associated neurocognitive disorders.Frontiers in neurologyPooled it
- Viral Infection and Connexin Dysfunction in the Heart.Current cardiology reports · 2025Review
- SIV infection induces alterations in gene expression and loss of interneurons in Rhesus Macaque frontal cortex during early systemic infection.Translational psychiatry · 2025Article
- Viruses and the Brain-A Relationship Prone to Trouble.Viruses · 2025Review
- The challenges to detect, quantify, and characterize viral reservoirs in the current antiretroviral era.NeuroImmune pharmacology and therapeutics · 2024Review
- Something to talk about; crosstalk disruption at the neurovascular unit during HIV infection of the CNS.NeuroImmune pharmacology and therapeutics · 2024Article
- Mechanisms of Intracellular Communication in Cancer and Pathogen Spreading.Results and problems in cell differentiation · 2024Review
- Humanized Mice for Studies of HIV-1 Persistence and Elimination.Pathogens (Basel, Switzerland) · 2023Review
- The role of tunneling nanotubes during early stages of HIV infection and reactivation: implications in HIV cure.NeuroImmune pharmacology and therapeutics · 2023Review
- Quantification of host proteomic responses to genotype 4 hepatitis E virus replication facilitated by pregnancy serum.Virology journal · 2023Article
- Identification, Quantification, and Characterization of HIV-1 Reservoirs in the Human Brain.Cells · 2022Article
- Review
- Roles of calpain in the apoptosis of Eimeria tenella host cells at the middle and late developmental stages.Parasitology research · 2022Article
- Direct Cell-Cell Communication via Membrane Pores, Gap Junction Channels, and Tunneling Nanotubes: Medical Relevance of Mitochondrial Exchange.International journal of molecular sciences · 2022Review
- The role of Pannexin-1 channels and extracellular ATP in the pathogenesis of the human immunodeficiency virus.Purinergic signalling · 2021Review
- HIV infection of astrocytes compromises inter-organelle interactions and inositol phosphate metabolism: A potential mechanism of bystander damage and viral reservoir survival.Progress in neurobiology · 2021Article
- Article
- Extracellular vesicles regulate gap junction-mediated intercellular communication and HIV-1 infection of human neural progenitor cells.Neurobiology of disease · 2021Article
- Astrocytes are HIV reservoirs in the brain: A cell type with poor HIV infectivity and replication but efficient cell-to-cell viral transfer.Journal of neurochemistry · 2021Article
- Gap Junction-Mediated Intercellular Communication of cAMP Prevents CDDP-Induced Ototoxicity via cAMP/PKA/CREB Pathway.International journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
HIV entry into the CNS is an early event after peripheral infection, resulting in neurologic dysfunction in a significant number of individuals despite successful anti-retroviral therapy. The mechanisms by which HIV mediates CNS dysfunction are not well understood. Our group recently demonstrated that HIV infection of astrocytes results in survival of HIV infected cells and apoptosis of surrounding uninfected astrocytes by the transmission of toxic intracellular signals through gap junctions. In the current report, we characterize the intracellular signaling responsible for this bystander apoptosis. Here, we demonstrate that HIV infection of astrocytes results in release of cytochrome C from the mitochondria into the cytoplasm, and dysregulation of inositol trisphosphate/intracellular calcium that leads to toxicity to neighboring uninfected astrocytes. Blocking these dysregulated pathways results in protection from bystander apoptosis. These secondary messengers that are toxic in uninfected cells are not toxic in HIV infected cells, suggesting that HIV protects these cells from apoptosis. Thus, our data provide novel mechanisms of HIV mediated toxicity and generation of HIV reservoirs. Our findings provide new potential therapeutic targets to reduce the CNS damage resulting from HIV infection and to eradicate the generation of viral reservoirs. We demonstrated that HIV infection of astrocytes protects infected cells from apoptosis but results in cell death of surrounding uninfected astrocytes by a mechanism that is dependent on gap junction channels, dysregulation of mitochondrial cytochrome C (CytC), and cell to cell diffusion of inositol trisphosphate (IP3 ) and calcium. Our data provide essential information about generation of brain reservoirs and the mechanism of toxicity mediated by the virus.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.