ArticleJournal of neurochemistry2014
HIV increases the release of dickkopf-1 protein from human astrocytes by a Cx43 hemichannel-dependent mechanism.
Article in Journal of neurochemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 76 citations in OpenAlex.
- Latent HIV Infection of BBB Pericytes Enhances Gap Junction-mediated Crosstalk with Endothelial Cells.Molecular neurobiology · 2026Article
- Latent HIV Infection of BBB Pericytes Disrupts Gap Junction-Mediated Crosstalk with Endothelial Cells.Research square · 2026Article
- Viral Infection and Connexin Dysfunction in the Heart.Current cardiology reports · 2025Review
- SARS-CoV-2 spike protein S1 activates Cx43 hemichannels and disturbs intracellular CaBiological research · 2023Article
- Identification of age-specific gene regulators of La Crosse virus neuroinvasion and pathogenesis.Nature communications · 2023Article
- Effects of Drugs Formerly Proposed for COVID-19 Treatment on Connexin43 Hemichannels.International journal of molecular sciences · 2022Article
- Contribution of large-pore channels to inflammation induced by microorganisms.Frontiers in cell and developmental biology · 2022Review
- HIV-1 gp120 Impairs Spatial Memory Through Cyclic AMP Response Element-Binding Protein.Frontiers in aging neuroscience · 2022Article
- 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
- Astroglial Hemichannels and Pannexons: The Hidden Link between Maternal Inflammation and Neurological Disorders.International journal of molecular sciences · 2021Review
- 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
- Extracellular vesicles regulate gap junction-mediated intercellular communication and HIV-1 infection of human neural progenitor cells.Neurobiology of disease · 2021Article
- In schizophrenia, non-remitters and partial remitters to treatment with antipsychotics are qualitatively distinct classes with respect to neurocognitive deficits and neuro-immune biomarkers: results of soft independent modeling of class analogy.Metabolic brain disease · 2021Article
- High Mobility Group Protein 1 and Dickkopf-Related Protein 1 in Schizophrenia and Treatment-Resistant Schizophrenia: Associations With Interleukin-6, Symptom Domains, and Neurocognitive Impairments.Schizophrenia bulletin · 2021Article
- Chronic fatigue syndrome and fibromyalgia-like symptoms are an integral component of the phenome of schizophrenia: neuro-immune and opioid system correlates.Metabolic brain disease · 2021Article
- HIV gp120 Protein Increases the Function of Connexin 43 Hemichannels and Pannexin-1 Channels in Astrocytes: Repercussions on Astroglial Function.International journal of molecular sciences · 2020Article
- Phylogeny of teleost connexins reveals highly inconsistent intra- and interspecies use of nomenclature and misassemblies in recent teleost chromosome assemblies.BMC genomics · 2020Article
- Astroglial connexins and cognition: memory formation or deterioration?Bioscience reports · 2020Review
- The Glutamate System as a Crucial Regulator of CNS Toxicity and Survival of HIV Reservoirs.Frontiers in cellular and infection microbiology · 2020Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Human immunodeficiency virus-1 (HIV) is a public health issue and a major complication of the disease is NeuroAIDS. In vivo, microglia/macrophages are the main cells infected. However, a low but significant number of HIV-infected astrocytes has also been detected, but their role in the pathogenesis of NeuroAIDS is not well understood. Our previous data indicate that gap junction channels amplify toxicity from few HIV-infected into uninfected astrocytes. Now, we demonstrated that HIV infection of astrocytes results in the opening of connexin43 hemichannels (HCs). HIV-induced opening of connexin43 HCs resulted in dysregulated secretion of dickkopf-1 protein (DKK1, a soluble wnt pathway inhibitor). Treatment of mixed cultures of neurons and astrocytes with DKK1, in the absence of HIV infection, resulted in the collapse of neuronal processes. HIV infection of mixed cultures of human neurons and astrocytes also resulted in the collapse of neuronal processes through a DKK1-dependent mechanism. In addition, dysregulated DKK1 expression in astrocytes was observed in human brain tissue sections of individuals with HIV encephalitis as compared to tissue sections from uninfected individuals. Thus, we demonstrated that HIV infection of astrocytes induces dysregulation of DKK1 by a HC-dependent mechanism that contributes to the brain pathogenesis observed in HIV-infected individuals. Our studies demonstrated that HIV infection of astrocytes, despite minimal replication and a low number of infected cells, induces dysregulation of DKK1 secretion by a Cx43 hemichannel (HC)-dependent mechanism. Enhanced DKK1 secretion in response to HIV infection of glial cells compromised formation and stability of neuronal processes, similar to the synaptic compromise observed in HIV-infected individuals. In addition, analysis of human brain tissue sections obtained from encephalitic individuals also shows enhanced expression of DKK1 in astrocytes. Our data provide a novel mechanism by which HIV infection of glial cells participate in the pathogenesis of brain dysfunction observed in HIV-infected individuals. LRP5 = Low-density lipoprotein receptor-related protein 5.
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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.