Purinergic Receptors: Key Mediators of HIV-1 Infection and Inflammation

Human immunodeficiency virus type 1 (HIV-1) causes a chronic infection that afflicts more than 30 million individuals worldwide. While the infection can be suppressed with potent antiretroviral therapies, individuals infected with HIV-1 have elevated levels of inflammation as indicated by increased T cell activation, soluble biomarkers, and associated morbidity and mortality. A single mechanism linking HIV-1 pathogenesis to this inflammation has yet to be identified. Purinergic receptors are known to mediate inflammation and have been shown to be required for HIV-1 infection at the level of HIV-1 membrane fusion. Here, we review the literature on the role of purinergic receptors in HIV-1 infection and associated inflammation and describe a role for these receptors as potential therapeutic targets.

• Publication year

  2015

• Venue

  Frontiers in Immunology

• Publication date

  2015-11-26

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.3389/fimmu.2015.00585PMID 26635799PMCID 4659914
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• High-Throughput HIV–Cell Fusion Assay for Discovery of Virus Entry Inhibitors

  2015cited by this paper
• P2X1 Receptor Antagonists Inhibit HIV-1 Fusion by Blocking Virus-Coreceptor Interactions

  2015influential reference
• Cell-to-Cell Transmission of HIV-1 Is Required to Trigger Pyroptotic Death of Lymphoid-Tissue-Derived CD4 T Cells.

  2015cited by this paper
• Synthesis of [(11)C]GSK1482160 as a new PET agent for targeting P2X(7) receptor.

  2015cited by this paper
• Pyroptotic cell death defends against intracellular pathogens

  2015influential reference
• Extracellular ATP induces the rapid release of HIV-1 from virus containing compartments of human macrophages

  2015cited by this paper
• HIV cell-to-cell transmission: effects on pathogenesis and antiretroviral therapy.

  2015cited by this paper
• Nucleoside reverse transcriptase inhibitors possess intrinsic anti-inflammatory activity

  2014cited by this paper
• HIV-1 Infection Induces Interleukin-1β Production via TLR8 Protein-dependent and NLRP3 Inflammasome Mechanisms in Human Monocytes*

  2014cited by this paper
• Highly Active Antiretroviral Therapies Are Effective against HIV-1 Cell-to-Cell Transmission

  2014cited by this paper
• Role of Pannexin-1 hemichannels and purinergic receptors in the pathogenesis of human diseases

  2014cited by this paper
• Unique Features of HIV-1 Spread through T Cell Virological Synapses

  2014cited by this paper
• Macrophages accumulate in the gut mucosa of untreated HIV-infected patients.

  2014cited by this paper
• The role of p2x7 receptor in infectious inflammatory diseases and the influence of ectonucleotidases

  2014cited by this paper
• The ACR20 and defining a threshold for response in rheumatic diseases: too much of a good thing

  2014cited by this paper
• A Meta-Analysis of P2X7 Gene-762T/C Polymorphism and Pulmonary Tuberculosis Susceptibility

  2014cited by this paper
• Microbial exposure alters HIV-1-induced mucosal CD4+ T cell death pathways Ex vivo

  2014cited by this paper
• IFI16 DNA Sensor Is Required for Death of Lymphoid CD4 T Cells Abortively Infected with HIV

  2014cited by this paper
• Nucleotide signalling during inflammation

  2014cited by this paper
• The effect of P2X7 receptor 1513 polymorphism on susceptibility to tuberculosis: A meta-analysis.

  2014cited by this paper
• Inflammatory cytokines drive CD4+ T-cell cycling and impaired responsiveness to interleukin 7: implications for immune failure in HIV disease.

  2014cited by this paper
• Gut epithelial barrier dysfunction and innate immune activation predict mortality in treated HIV infection.

  2014cited by this paper
• Putative roles of purinergic signaling in human immunodeficiency virus-1 infection

  2014cited by this paper
• The Semen Microbiome and Its Relationship with Local Immunology and Viral Load in HIV Infection

  2014cited by this paper
• Soluble markers of inflammation and coagulation but not T-cell activation predict non-AIDS-defining morbid events during suppressive antiretroviral treatment.

  2014cited by this paper
• P2X-Selective Purinergic Antagonists Are Strong Inhibitors of HIV-1 Fusion during both Cell-to-Cell and Cell-Free Infection

  2014cited by this paper
• Editorial: Pannexin‐1—the hidden gatekeeper for HIV‐1

  2013cited by this paper
• Pharmacokinetic and pharmacodynamic profiling of a P2X7 receptor allosteric modulator GSK1482160 in healthy human subjects.

  2013influential reference
• Long-Term Heart Transplant Survival by Targeting the Ionotropic Purinergic Receptor P2X7

  2013cited by this paper
• Transcript Analysis of P2X Receptors in PBMCs of Chronic HCV Patients: An Insight into Antiviral Treatment Response and HCV-Induced Pathogenesis

  2013cited by this paper
• Adenosine Triphosphate Released from HIV-Infected Macrophages Regulates Glutamatergic Tone and Dendritic Spine Density on Neurons

  2013cited by this paper
• Proteoglycans Act as Cellular Hepatitis Delta Virus Attachment Receptors

  2013cited by this paper
• Pannexin1 hemichannels are critical for HIV infection of human primary CD4+ T lymphocytes

  2013cited by this paper
• P2X7 Receptor Channels Allow Direct Permeation of Nanometer-Sized Dyes

  2013cited by this paper
• Ligand-Gated Purinergic Receptors Regulate HIV-1 Tat and Morphine Related Neurotoxicity in Primary Mouse Striatal Neuron-Glia Co-Cultures

  2013cited by this paper
• Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection

  2013cited by this paper
• Purinergic P2X7 Receptor Drives T Cell

  2012cited by this paper
• Inflammasomes and their roles in health and disease.

  2012cited by this paper
• NLRs, inflammasomes, and viral infection

  2012cited by this paper
• Purinergic signalling: Its unpopular beginning, its acceptance and its exciting future

  2012cited by this paper
• Purinergic P2X7 Receptor Drives T Cell Lineage Choice and Shapes Peripheral γδ Cells

  2012cited by this paper
• ATP release and autocrine signaling through P2X4 receptors regulate gamma delta T cell activation

  2012cited by this paper
• P2X7 receptors: channels, pores and more.

  2012cited by this paper
• Activation of P2X7 Receptor by ATP Plays an Important Role in Regulating Inflammatory Responses during Acute Viral Infection

  2012cited by this paper
• Purinergic signaling during inflammation.

  2012cited by this paper
• ATP release and autocrine signaling through P2X4 receptors regulate γδ T cell activation

  2012cited by this paper
• Efficacy and Safety of CE-224,535, an Antagonist of P2X7 Receptor, in Treatment of Patients with Rheumatoid Arthritis Inadequately Controlled by Methotrexate

  2012cited by this paper
• The role of lipopolysaccharide as a marker of immune activation in HIV-1 infected patients: a systematic literature review

  2012cited by this paper
• Clinical evaluation of the efficacy of the P2X7 purinergic receptor antagonist AZD9056 on the signs and symptoms of rheumatoid arthritis in patients with active disease despite treatment with methotrexate or sulphasalazine

  2012cited by this paper
• P2X7 receptor regulation of non‐classical secretion from immune effector cells

  2012cited by this paper
• Multifaceted roles of purinergic receptors in viral infection.

  2012cited by this paper
• Aging, inflammation, and HIV infection.

  2012cited by this paper
• Regulation of leukocyte function by adenosine receptors.

  2011cited by this paper
• HIV infection, inflammation, immunosenescence, and aging.

  2011cited by this paper
• Activation and Regulation of Purinergic P2X Receptor Channels

  2011cited by this paper
• The Role of the P2X7 Receptor in Infectious Diseases

  2011cited by this paper
• Identification of ionotrophic purinergic receptors in Huh-7 cells and their response towards structural proteins of HCV genotype 3a

  2011cited by this paper
• Premature age-related comorbidities among HIV-infected persons compared with the general population.

  2011cited by this paper
• Extracellular ATP acts on P2Y2 purinergic receptors to facilitate HIV-1 infection

  2011cited by this paper
• Differential Modulation of ATP-Induced P2X7-Associated Permeabilities to Cations and Anions of Macrophages by Infection with Leishmania amazonensis

  2011cited by this paper
• Immune cell regulation by autocrine purinergic signalling

  2011cited by this paper
• A potential therapeutic role for P2X7 receptor (P2X7R) antagonists in the treatment of inflammatory diseases

  2011cited by this paper
• CD39/Adenosine Pathway Is Involved in AIDS Progression

  2011cited by this paper
• Purinergic signalling: pathophysiology and therapeutic potential.

  2011cited by this paper
• Optimization of the physicochemical and pharmacokinetic attributes in a 6-azauracil series of P2X7 receptor antagonists leading to the discovery of the clinical candidate CE-224,535.

  2011cited by this paper
• Immunologic failure despite suppressive antiretroviral therapy is related to activation and turnover of memory CD4 cells.

  2011cited by this paper
• Infection with Leishmania amazonensis upregulates purinergic receptor expression and induces host‐cell susceptibility to UTP‐mediated apoptosis

  2011cited by this paper
• ATP Inhibits the Generation and Function of Regulatory T Cells Through the Activation of Purinergic P2X Receptors

  2011cited by this paper
• P2X receptors in health and disease.

  2011cited by this paper
• A randomized, controlled trial of raltegravir intensification in antiretroviral-treated, HIV-infected patients with a suboptimal CD4+ T cell response.

  2011cited by this paper
• Cancer Screening in Patients Infected with HIV

  2011cited by this paper
• When to Initiate Combined Antiretroviral Therapy to Reduce Mortality and AIDS-Defining Illness in HIV-Infected Persons in Developed Countries

  2011cited by this paper
• Soluble CD163 made by monocyte/macrophages is a novel marker of HIV activity in early and chronic infection prior to and after anti-retroviral therapy.

  2011cited by this paper
• Dysregulation of the inflammatory response to the parasite, Toxoplasma gondii, in P2X7 receptor-deficient mice.

  2011cited by this paper
• Molecular pharmacology, physiology, and structure of the P2Y receptors.

  2011cited by this paper
• Purinergic signaling: a novel mechanism in immune surveillance

  2010cited by this paper
• CD4 T-cell hyperactivation and susceptibility to cell death determine poor CD4 T-cell recovery during suppressive HAART

  2010cited by this paper
• Purinergic Receptor Functionality Is Necessary for Infection of Human Hepatocytes by Hepatitis Delta Virus and Hepatitis B Virus

  2010cited by this paper
• Markers of inflammation, coagulation, and renal function are elevated in adults with HIV infection.

  2010cited by this paper
• Abortive HIV infection mediates CD4 T cell depletion and inflammation in human lymphoid tissue.

  2010cited by this paper
• P2X7 Receptor-Mediated Killing of an Intracellular Parasite, Toxoplasma gondii, by Human and Murine Macrophages

  2010cited by this paper
• Metaanalysis of P2X7 gene polymorphisms and tuberculosis susceptibility.

  2010cited by this paper
• Intravascular Danger Signals Guide Neutrophils to Sites of Sterile Inflammation

  2010cited by this paper
• IL-1β Processing in Host Defense: Beyond the Inflammasomes

  2010cited by this paper
• Autocrine Purinergic Receptor Signaling Is Essential for Macrophage Chemotaxis

  2010cited by this paper
• Treatment intensification does not reduce residual HIV-1 viremia in patients on highly active antiretroviral therapy

  2009cited by this paper
• Association of the purinergic receptor P2Y, G-protein coupled, 2 (P2RY2) gene with myocardial infarction in Japanese men.

  2009cited by this paper
• Autocrine regulation of T‐cell activation by ATP release and P2X7 receptors

  2009cited by this paper
• Signaling at purinergic P2X receptors.

  2009cited by this paper
• Activation of the NLRP3 inflammasome in dendritic cells induces IL-1β–dependent adaptive immunity against tumors

  2009cited by this paper
• A Meta-Analysis

  2009cited by this paper
• P2X7 Receptor-Stimulated Secretion of MHC Class II-Containing Exosomes Requires the ASC/NLRP3 Inflammasome but Is Independent of Caspase-1 1

  2009cited by this paper
• Serum immune activation markers are persistently increased in patients with HIV infection after 6 years of antiretroviral therapy despite suppression of viral replication and reconstitution of CD4+ T cells.

  2009cited by this paper
• ATP-gated P2X cation-channels.

  2009cited by this paper
• Pyroptosis: host cell death and inflammation

  2009cited by this paper
• Determination of the Underlying Cause of Death in Three Multicenter International HIV Clinical Trials

  2008cited by this paper
• Extracellular ATP reduces HIV-1 transfer from immature dendritic cells to CD4+ T lymphocytes

  2008cited by this paper
• Purinergic signalling and disorders of the central nervous system

  2008cited by this paper
• Selective P2X7 receptor antagonists for chronic inflammation and pain

  2008cited by this paper
• Effect of the Purinergic Receptor P2X7 on Chlamydia Infection in Cervical Epithelial Cells and Vaginally Infected Mice1

  2007cited by this paper

• Beyond viral suppression: decoding the mitochondrial-immune axis in HIV-associated inflammation and immune dysfunction

  2025influential citation
• The impacts of tobacco and nicotine on HIV-1 infection, inflammation, and the blood-brain barrier in the central nervous system

  2024cites this paper
• Prevalence of Age-Related Macular Degeneration in Patients with Chronic Exposure to P2X7R Inhibitors

  2024cites this paper
• Oxidative phosphorylation in HIV-1 infection: impacts on cellular metabolism and immune function

  2024cites this paper
• The impact of cannabinoids on inflammasome signaling in HIV-1 infection

  2023cites this paper
• The role of extracellular ATP and P2X receptors in the pathogenesis of HIV-1.

  2023cites this paper
• Pentraxin 3 as an Immune Recovery Marker in HIV Infection After Combination Antiretroviral Therapy

  2023cites this paper
• HIV-1 activates oxidative phosphorylation in infected CD4 T cells in a human tonsil explant model

  2023cites this paper
• The Possible Therapeutic Application of CO on COVID-19

  2023cites this paper
• Inflammasomes as mediators of inflammation in HIV-1 infection.

  2022cites this paper
• HIV-1 infection of human tonsils activates CD4+ T cell oxidative phosphorylation and myeloid NLRP3 in ammasome activation

  2022cites this paper
• The ATP-dependent pathways and human diseases.

  2022cites this paper
• Single-Cell Characterization of Calcium Influx and HIV-1 Infection using a Multiparameter Optofluidic Platform.

  2021cites this paper
• P2RX7 at the Host-Pathogen Interface of Infectious Diseases

  2021influential citation
• Human immunodeficiency virus‐1/simian immunodeficiency virus infection induces opening of pannexin‐1 channels resulting in neuronal synaptic compromise: A novel therapeutic opportunity to prevent NeuroHIV

  2021cites this paper
• P2X7 receptor in multifaceted cellular signaling and its relevance as a potential therapeutic target in different diseases.

  2021cites this paper
• The role of Pannexin-1 channels and extracellular ATP in the pathogenesis of the human immunodeficiency virus

  2021cites this paper
• The Adenosine Pathway and Human Immunodeficiency Virus-Associated Inflammation

  2021cites this paper
• The Adenosine Pathway and HIV-Associated Inflammation

  2021cites this paper
• NLRP3 Inflammasome Signaling as a Link Between HIV-1 Infection and Atherosclerotic Cardiovascular Disease

  2020cites this paper
• Ca2+‐dependent release of ATP from astrocytes affects herpes simplex virus type 1 infection of neurons

  2020cites this paper
• Inflammatory and immunometabolic consequences of gut dysfunction in HIV: Parallels with IBD and implications for reservoir persistence and non-AIDS comorbidities

  2019cites this paper
• The role of platelets in the regulation of pulmonary infection and host defence

  2019cites this paper
• Potential Therapeutic Applications of P2 Receptor Antagonists: from Bench to Clinical Trials.

  2019cites this paper
• The Role of Purinergic P2X and P2Y Receptors in Hearing Loss

  2018cites this paper
• The P2X7 Receptor in Inflammatory Diseases: Angel or Demon?

  2018cites this paper
• Novel and differentially abundant microRNAs in sperm cells, seminal plasma, and serum of boars due to porcine reproduction and respiratory syndrome virus infection.

  2018cites this paper
• Purinergic receptors and neglected tropical diseases: why ignore purinergic signaling in the search for new molecular targets?

  2018cites this paper
• The potential of P2X7 receptors as a therapeutic target, including inflammation and tumour progression

  2017cites this paper
• The P2X7 receptor: A main player in inflammation

  2017cites this paper
• HIV Alters Gap Junction-Mediated Intercellular Communication in Human Brain Pericytes

  2017cites this paper
• Purinergic drug targets for gastrointestinal disorders

  2017cites this paper
• MicroRNAs Modulate the Purinergic Signaling Network.

  2016cites this paper