ArticleProceedings of the National Academy of Sciences of the United States of America2000
HIV-1 gp120 and chemokines activate ion channels in primary macrophages through CCR5 and CXCR4 stimulation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 149 citations in OpenAlex.
- Targeting of specific CCR5-G protein complexes underlies biased signaling by HIV-1 envelope glycoproteins.Cell communication and signaling : CCS · 2025Article
- Pannexin-1 channels, extracellular ATP, and purinergic receptors are essential for CCR5/CXCR4 clustering and HIV entry.NeuroImmune pharmacology and therapeutics · 2025Article
- Viruses and the Brain-A Relationship Prone to Trouble.Viruses · 2025Review
- Respiratory syncytial virus glycoprotein G impedes CXNpj viruses · 2024Article
- Cooperative interactions between neurotrophin receptors and CXCR4 regulate macrophage phenotype and susceptibility to activation by HIV.Journal of neurovirology · 2024Article
- Multi-omic longitudinal study reveals immune correlates of clinical course among hospitalized COVID-19 patients.Cell reports. Medicine · 2023Article
- Co-receptor signaling in the pathogenesis of neuroHIV.Retrovirology · 2021Review
- Modeling of CCR5 Recognition by HIV-1 gp120: How the Viral Protein Exploits the Conformational Plasticity of the Coreceptor.Viruses · 2021Article
- HIV Neuropathogenesis in the Presence of a Disrupted Dopamine System.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2020Review
- Dopamine increases HIV entry into macrophages by increasing calcium release via an alternative signaling pathway.Brain, behavior, and immunity · 2019Article
- The role of catecholamines in HIV neuropathogenesis.Brain research · 2019Review
- Nicotinic Acetylcholine Receptors in HIV: Possible Roles During HAND and Inflammation.Cellular and molecular neurobiology · 2018Review
- The alpha7-nicotinic receptor contributes to gp120-induced neurotoxicity: implications in HIV-associated neurocognitive disorders.Scientific reports · 2018Article
- Pannexin1 Channels Are Required for Chemokine-Mediated Migration of CD4+ T Lymphocytes: Role in Inflammation and Experimental Autoimmune Encephalomyelitis.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- Syncytial apoptosis signaling network induced by the HIV-1 envelope glycoprotein complex: an overview.Cell death & disease · 2015Review
- HIV-1 gp120 influences the expression of microRNAs in human monocyte-derived dendritic cells via STAT3 activation.BMC genomics · 2015Article
- Mechanisms of distal axonal degeneration in peripheral neuropathies.Neuroscience letters · 2015Review
- Role of the macrophage in HIV-associated neurocognitive disorders and other comorbidities in patients on effective antiretroviral treatment.Journal of neurovirology · 2015Review
- Ion channels in innate and adaptive immunity.Annual review of immunology · 2015Review
- HIV-1 gp120 activates the STAT3/interleukin-6 axis in primary human monocyte-derived dendritic cells.Journal of virology · 2014Article
13 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
HIV type 1 (HIV-1) uses the chemokine receptors CCR5 and CXCR4 as coreceptors for entry into target cells. Here we show that the HIV-1 envelope gp120 (Env) activates multiple ionic signaling responses in primary human macrophages, which are important targets for HIV-1 in vivo. Env from both CCR5-dependent JRFL (R5) and CXCR4-dependent IIIB (X4) HIV-1 opened calcium-activated potassium (K(Ca)), chloride, and calcium-permeant nonselective cation channels in macrophages. These signals were mediated by CCR5 and CXCR4 because macrophages lacking CCR5 failed to respond to JRFL and an inhibitor of CXCR4 blocked ion current activation by IIIB. MIP-1beta and SDF-1alpha, chemokine ligands for CCR5 and CXCR4, respectively, also activated K(Ca) and Cl(-) currents in macrophages, but nonselective cation channel activation was unique to gp120. Intracellular Ca(2+) levels were also elevated by gp120. The patterns of activation mediated by CCR5 and CXCR4 were qualitatively similar but quantitatively distinct, as R5 Env activated the K(Ca) current more frequently, elicited Cl(-) currents that were approximately 2-fold greater in amplitude, and elevated intracellular Ca(+2) to higher peak and steady-state levels. Env from R5 and X4 primary isolates evoked similar current responses as the corresponding prototype strains. Thus, the interaction of HIV-1 gp120 with CCR5 or CXCR4 evokes complex and distinct signaling responses in primary macrophages, and gp120-evoked signals differ from those activated by the coreceptors' chemokine ligands. Intracellular signaling responses of macrophages to HIV-1 may modulate postentry steps of infection and cell functions apart from infection.
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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.