Extracellular ATP acts on P2Y2 purinergic receptors to facilitate HIV-1 infection

Séror, Claire; Melki, Marie Thérèse; Subra, Frédéric; Raza, Syed Qasim; Bras, Marlène; Saïdi, Héla; Nardacci, Roberta; Voisin, Laurent; Paoletti, Audrey; Law, Frédéric; Martins, Isabelle; Amendola, Alessandra; Abdul-Sater, Ali A.; Ciccosanti, Fabiola; Delelis, Olivier; Niedergang, Florence; Thierry, Sylvain; Saïd-Sadier, Najwane; Lamaze, Christophe; Métivier, Didier; Estaquier, Jérǒme; Fimia, Gian María; Falasca, Laura; Casetti, Rita; Modjtahedi, Nazanine; Kanellopoulos, Jean; Mouscadet, Jean François; Ojcius, David M.; Piacentini, Mauro; Gougeon, Marie Lise; Kroemer, Guido; Perfettini, Jean-Luc

doi:10.1084/jem.20101805

Cited by 156 publications

(179 citation statements)

References 50 publications

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“…Published studies implicate the P2X1 receptor in HIV-1 entry/fusion and in cell-cell transmission. 67,68,80 However, the mechanism by which these channels modulate HIV-1 fusion remains unclear. Purinergic receptors are widely distributed in the central nervous system and in many peripheral tissues and are classified into two main classes, P1 receptors that bind adenosine, and P2 receptors that are responsive to phosphorylated nucleosides, such as ATP, ADP, and related nucleotides.…”

Section: Discussionmentioning

confidence: 99%

“…Purinergic receptors have been previously reported to play a role in HIV-1 fusion and infection in macrophages and CD4 + T cells. 67,68 The authors proposed that purinergic receptors are involved in a signaling cascade that leads to elevation of the cytosolic calcium, which in turn promotes HIV-1 fusion through an unknown mechanism. To determine the types of purinergic receptors required for HIV-1 fusion with target cells, we used a panel of specific inhibitors of P2X and P2Y receptors.…”

Section: Inhibitors Of P2x1 Receptor Interfere With Hiv-1 Fusionmentioning

confidence: 99%

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

Marin

Giroud

et al. 2015

ASSAY and Drug Development Technologies

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HIV-1 initiates infection by merging its envelope membrane with the target cell membrane, a process that is mediated by the viral Env glycoprotein following its sequential binding to CD4 and coreceptors, CXCR4 or CCR5. Although HIV-1 fusion has been a target for antiviral therapy, the virus has developed resistance to drugs blocking the CCR5 binding or Env refolding steps of this process. This highlights the need for novel inhibitors. Here, we adapted and optimized an enzymatic HIV-cell fusion assay, which reports the transfer of virus-encapsulated b-lactamase into the cytoplasm, to high-throughput screening (HTS) with a 384-well format. The assay was robustly performed in HTS format and was validated by the pilot screen of a small library of pharmacologically active compounds. Several hits identified by screening included a prominent cluster of purinergic receptor antagonists. Functional studies demonstrated that P2X1 receptor antagonists selectively inhibited HIV-1 fusion without affecting the fusion activity of an unrelated virus that enters cells through an endocytic route. The inhibition of HIV-cell fusion by P2X1 antagonists was not through downmodulation of the cell surface expression of CD4 or coreceptors, thus implicating P2X1 receptor in the HIV-1 fusion step. The ability of these antagonists to inhibit viruses regardless of their coreceptor (CXCR4 or CCR5) preference indicates that fusion is blocked at a late step downstream of coreceptor binding. A future large-scale screening campaign for HIV-1 fusion inhibitors, using the above functional readout, will likely reveal novel classes of inhibitors and suggest potential targets for antiviral therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Inhibitors Of P2x1 Receptor Interfere With Hiv-1 Fusionmentioning

confidence: 99%

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

Marin

Giroud

et al. 2015

ASSAY and Drug Development Technologies

View full text Add to dashboard Cite

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“…9,65 Unlike ecto-CRT induction, the release of ATP and HMGB1 is triggered by a range of death-inducing stimuli, and is not restricted to induction in apoptotic cell death. 47 Although ATP production is required for efficient vaccinia virus production 71 and facilitates HIV infection through its interaction with P2Y2 receptors, 72 there is little knowledge of how oncolytic viruses provoke ATP release.…”

Section: Adenosine Triphosphatementioning

confidence: 99%

Multimodal immunogenic cancer cell death as a consequence of anticancer cytotoxic treatments

2013

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Apoptotic cell death generally characterized by a morphologically homogenous entity has been considered to be essentially non-immunogenic. However, apoptotic cancer cell death, also known as type 1 programmed cell death (PCD), was recently found to be immunogenic after treatment with several chemotherapeutic agents and oncolytic viruses through the emission of various danger-associated molecular patterns (DAMPs). Extensive studies have revealed that two different types of immunogenic cell death (ICD) inducers, recently classified by their distinct actions in endoplasmic reticulum (ER) stress, can reinitiate immune responses suppressed by the tumor microenvironment. Indeed, recent clinical studies have shown that several immunotherapeutic modalities including therapeutic cancer vaccines and oncolytic viruses, but not conventional chemotherapies, culminate in beneficial outcomes, probably because of their different mechanisms of ICD induction. Furthermore, interests in PCD of cancer cells have shifted from its classical form to novel forms involving autophagic cell death (ACD), programmed necrotic cell death (necroptosis), and pyroptosis, some of which entail immunogenicity after anticancer treatments. In this review, we provide a brief outline of the well-characterized DAMPs such as calreticulin (CRT) exposure, high-mobility group protein B1 (HMGB1), and adenosine triphosphate (ATP) release, which are induced by the morphologically distinct types of cell death. In the latter part, our review focuses on how emerging oncolytic viruses induce different forms of cell death and the combinations of oncolytic virotherapies with further immunomodulation by cyclophosphamide and other immunotherapeutic modalities foster dendritic cell (DC)-mediated induction of antitumor immunity. Accordingly, it is increasingly important to fully understand how and which ICD inducers cause multimodal ICD, which should aid the design of reasonably multifaceted anticancer modalities to maximize ICD-triggered antitumor immunity and eliminate residual or metastasized tumors while sparing autoimmune diseases.

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“…A number of studies followed indicating that pharmacological inhibitors of Panx1 reduced ATP release in a broad range of cells, including lung epithelial cells [151][152][153], hypoxic red cells [154][155][156], bovine ciliary epithelial cells [157], retina and trabecular meshwork (TM5) cells [158,159], skeletal muscle [160], taste bud cells [161], T lymphocytes [61,62,162], and human neutrophils [109]. Panx1 knockdown (siRNA or shRNA) reduced nucleotide release in hypotonic-stressstimulated airway epithelial cells [151,152], stretched cardiomyocytes [163], apoptotic T lymphocytes [162] and T cells undergoing HIV infection [164], TM5 cells [159], and astrocytes [165]. Conversely, overexpression of Panx1 resulted in enhanced release of ATP from apoptotic Jurkat cells [162] and hypotonically swollen human embryonic kidney (HEK) 293 cells [159].…”

Section: Pannexinsmentioning

confidence: 99%

Vesicular and conductive mechanisms of nucleotide release

Lazarowski

2012

Purinergic Signalling

254

225

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Extracellular nucleotides and nucleosides promote a vast range of physiological responses, via activation of cell surface purinergic receptors. Virtually all tissues and cell types exhibit regulated release of ATP, which, in many cases, is accompanied by the release of uridine nucleotides. Given the relevance of extracellular nucleotide/nucleoside-evoked responses, understanding how ATP and other nucleotides are released from cells is an important physiological question. By facilitating the entry of cytosolic nucleotides into the secretory pathway, recently identified vesicular nucleotide and nucleotide-sugar transporters contribute to the exocytotic release of ATP and UDP-sugars not only from endocrine/exocrine tissues, but also from cell types in which secretory granules have not been biochemically characterized. In addition, plasma membrane connexin hemichannels, pannexin channels, and less-well molecularly defined ATP conducting anion channels have been shown to contribute to the release of ATP (and UTP) under a variety of conditions.

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Extracellular ATP acts on P2Y2 purinergic receptors to facilitate HIV-1 infection

Abstract: Contact with HIV-1 envelope protein elicits release of ATP through pannexin-1 channels on target cells; by activating purinergic receptors and Pyk2 kinase in target cells, this extracellular ATP boosts HIV-1 infectivity.

Cited by 156 publications

References 50 publications

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

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

Multimodal immunogenic cancer cell death as a consequence of anticancer cytotoxic treatments

Vesicular and conductive mechanisms of nucleotide release

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