HIV-1 Envelope Overcomes NLRP3-Mediated Inhibition of F-Actin Polymerization for Viral Entry
Summary: Purinergic receptors and nucleotide-binding domain leucine-rich repeat containing (NLR) proteins have been shown to control viral infection. Here, we show that the NLR family member NLRP3 and the purinergic receptor P2Y2 constitutively interact and regulate susceptibility to HIV-1 infection...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-09-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124719302815 |
| _version_ | 1819168807582695424 |
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| author | Audrey Paoletti Awatef Allouch Marina Caillet Hela Saïdi Frédéric Subra Roberta Nardacci Qiuji Wu Zeinaf Muradova Laurent Voisin Syed Qasim Raza Frédéric Law Maxime Thoreau Haithem Dakhli Olivier Delelis Béatrice Poirier-Beaudouin Nathalie Dereuddre-Bosquet Roger Le Grand Olivier Lambotte Asier Saez-Cirion Gianfranco Pancino David M. Ojcius Eric Solary Eric Deutsch Mauro Piacentini Marie-Lise Gougeon Guido Kroemer Jean-Luc Perfettini |
| author_facet | Audrey Paoletti Awatef Allouch Marina Caillet Hela Saïdi Frédéric Subra Roberta Nardacci Qiuji Wu Zeinaf Muradova Laurent Voisin Syed Qasim Raza Frédéric Law Maxime Thoreau Haithem Dakhli Olivier Delelis Béatrice Poirier-Beaudouin Nathalie Dereuddre-Bosquet Roger Le Grand Olivier Lambotte Asier Saez-Cirion Gianfranco Pancino David M. Ojcius Eric Solary Eric Deutsch Mauro Piacentini Marie-Lise Gougeon Guido Kroemer Jean-Luc Perfettini |
| author_sort | Audrey Paoletti |
| collection | DOAJ |
| description | Summary: Purinergic receptors and nucleotide-binding domain leucine-rich repeat containing (NLR) proteins have been shown to control viral infection. Here, we show that the NLR family member NLRP3 and the purinergic receptor P2Y2 constitutively interact and regulate susceptibility to HIV-1 infection. We found that NLRP3 acts as an inhibitory factor of viral entry that represses F-actin remodeling. The binding of the HIV-1 envelope to its host cell receptors (CD4, CXCR4, and/or CCR5) overcomes this restriction by stimulating P2Y2. Once activated, P2Y2 enhances its interaction with NLRP3 and stimulates the recruitment of the E3 ubiquitin ligase CBL to NLRP3, ultimately leading to NLRP3 degradation. NLRP3 degradation is permissive for PYK2 phosphorylation (PYK2Y402∗) and subsequent F-actin polymerization, which is required for the entry of HIV-1 into host cells. Taken together, our results uncover a mechanism by which HIV-1 overcomes NLRP3 restriction that appears essential for the accomplishment of the early steps of HIV-1 entry. : Paoletti et al. identified a constitutive interaction between NLRP3 and P2Y2 that regulates HIV-1 entry into target cells. They revealed that NLRP3 represses viral entry by impairing F-actin reorganization. HIV-1 overcomes this host cellular resistance by inducing NLRP3 degradation through the activation of P2Y2-dependent signaling pathway. Keywords: NLRP3, P2Y2, CBL, inflammasome, viral entry, HIV |
| first_indexed | 2024-12-22T19:09:28Z |
| format | Article |
| id | doaj.art-c7adf53f201d44c8aeb0a6f00c2f5981 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-22T19:09:28Z |
| publishDate | 2019-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-c7adf53f201d44c8aeb0a6f00c2f59812022-12-21T18:15:42ZengElsevierCell Reports2211-12472019-09-01281333813394.e7HIV-1 Envelope Overcomes NLRP3-Mediated Inhibition of F-Actin Polymerization for Viral EntryAudrey Paoletti0Awatef Allouch1Marina Caillet2Hela Saïdi3Frédéric Subra4Roberta Nardacci5Qiuji Wu6Zeinaf Muradova7Laurent Voisin8Syed Qasim Raza9Frédéric Law10Maxime Thoreau11Haithem Dakhli12Olivier Delelis13Béatrice Poirier-Beaudouin14Nathalie Dereuddre-Bosquet15Roger Le Grand16Olivier Lambotte17Asier Saez-Cirion18Gianfranco Pancino19David M. Ojcius20Eric Solary21Eric Deutsch22Mauro Piacentini23Marie-Lise Gougeon24Guido Kroemer25Jean-Luc Perfettini26Cell Death and Aging Team, Gustave Roussy, 114 rue Edouard Vaillant, F-94805 Villejuif, France; Laboratory of Molecular Radiotherapy, INSERM U1030, Gustave Roussy, 114 rue Edouard Vaillant, F-94805 Villejuif, France; Gustave Roussy, 114 rue Edouard Vaillant, F-94805 Villejuif, France; Université Paris Sud - Paris 11, 114 rue Edouard Vaillant, F-94805 Villejuif, FranceCell Death and Aging Team, Gustave Roussy, 114 rue Edouard Vaillant, F-94805 Villejuif, France; Laboratory of Molecular Radiotherapy, INSERM U1030, Gustave Roussy, 114 rue Edouard Vaillant, F-94805 Villejuif, France; Gustave Roussy, 114 rue Edouard Vaillant, F-94805 Villejuif, France; Université Paris Sud - Paris 11, 114 rue Edouard Vaillant, F-94805 Villejuif, FranceGustave Roussy, 114 rue Edouard Vaillant, F-94805 Villejuif, France; Université Paris Sud - Paris 11, 114 rue Edouard Vaillant, F-94805 Villejuif, France; INSERM U848, Gustave Roussy, 114 rue Edouard Vaillant, F-94805 Villejuif, FranceInstitut Pasteur, Antiviral Immunity, Biotherapy and Vaccine Unit, Infection and Epidemiology Department, 25 rue du Dr. Roux, F-75015 Paris, FranceCNRS UMR 8113 LBPA, Ecole Normale Supérieure de Cachan, 61 avenue du Président Wilson, F-94230 Cachan, FranceNational Institute for Infectious Diseases “Lazzaro Spallanzani,”, Via Portuense 292, 00149 Rome, ItalyCell Death and Aging Team, Gustave Roussy, 114 rue Edouard Vaillant, F-94805 Villejuif, France; Laboratory of Molecular Radiotherapy, INSERM U1030, Gustave Roussy, 114 rue Edouard Vaillant, F-94805 Villejuif, France; Gustave Roussy, 114 rue Edouard Vaillant, F-94805 Villejuif, France; Université Paris Sud - Paris 11, 114 rue Edouard Vaillant, F-94805 Villejuif, FranceCell Death and Aging Team, Gustave Roussy, 114 rue Edouard Vaillant, F-94805 Villejuif, France; Laboratory of Molecular Radiotherapy, INSERM U1030, Gustave Roussy, 114 rue Edouard Vaillant, F-94805 Villejuif, France; Gustave Roussy, 114 rue Edouard Vaillant, F-94805 Villejuif, France; Université Paris Sud - Paris 11, 114 rue Edouard Vaillant, F-94805 Villejuif, FranceCell Death and Aging Team, Gustave Roussy, 114 rue Edouard Vaillant, F-94805 Villejuif, France; Laboratory of Molecular Radiotherapy, INSERM U1030, Gustave Roussy, 114 rue Edouard Vaillant, F-94805 Villejuif, France; Gustave Roussy, 114 rue Edouard Vaillant, F-94805 Villejuif, France; Université Paris Sud - Paris 11, 114 rue Edouard Vaillant, F-94805 Villejuif, FranceCell Death and Aging Team, Gustave Roussy, 114 rue Edouard Vaillant, F-94805 Villejuif, France; Laboratory of Molecular Radiotherapy, INSERM U1030, Gustave Roussy, 114 rue Edouard Vaillant, F-94805 Villejuif, France; Gustave Roussy, 114 rue Edouard Vaillant, F-94805 Villejuif, France; Université Paris Sud - Paris 11, 114 rue Edouard Vaillant, F-94805 Villejuif, FranceCell Death and Aging Team, Gustave Roussy, 114 rue Edouard Vaillant, F-94805 Villejuif, France; Laboratory of Molecular Radiotherapy, INSERM U1030, Gustave Roussy, 114 rue Edouard Vaillant, F-94805 Villejuif, France; Gustave Roussy, 114 rue Edouard Vaillant, F-94805 Villejuif, France; Université Paris Sud - Paris 11, 114 rue Edouard Vaillant, F-94805 Villejuif, FranceCell Death and Aging Team, Gustave Roussy, 114 rue Edouard Vaillant, F-94805 Villejuif, France; Laboratory of Molecular Radiotherapy, INSERM U1030, Gustave Roussy, 114 rue Edouard Vaillant, F-94805 Villejuif, France; Gustave Roussy, 114 rue Edouard Vaillant, F-94805 Villejuif, France; Université Paris Sud - Paris 11, 114 rue Edouard Vaillant, F-94805 Villejuif, FranceCell Death and Aging Team, Gustave Roussy, 114 rue Edouard Vaillant, F-94805 Villejuif, France; Laboratory of Molecular Radiotherapy, INSERM U1030, Gustave Roussy, 114 rue Edouard Vaillant, F-94805 Villejuif, France; Gustave Roussy, 114 rue Edouard Vaillant, F-94805 Villejuif, France; Université Paris Sud - Paris 11, 114 rue Edouard Vaillant, F-94805 Villejuif, FranceCNRS UMR 8113 LBPA, Ecole Normale Supérieure de Cachan, 61 avenue du Président Wilson, F-94230 Cachan, FranceInstitut Pasteur, Antiviral Immunity, Biotherapy and Vaccine Unit, Infection and Epidemiology Department, 25 rue du Dr. Roux, F-75015 Paris, FranceINSERM U1184, Center for Immunology of Viral Infections and Autoimmune Diseases, Fontenay-aux-Roses, France; Université Paris Sud, UMR 1184, Fontenay-aux-Roses, France; CEA, DSV/iMETI, Division of Immunology-Virology, IDMIT, Fontenay-aux-Roses, FranceINSERM U1184, Center for Immunology of Viral Infections and Autoimmune Diseases, Fontenay-aux-Roses, France; Université Paris Sud, UMR 1184, Fontenay-aux-Roses, France; CEA, DSV/iMETI, Division of Immunology-Virology, IDMIT, Fontenay-aux-Roses, FranceINSERM U1184, Center for Immunology of Viral Infections and Autoimmune Diseases, Fontenay-aux-Roses, France; CEA, DSV/iMETI, Division of Immunology-Virology, IDMIT, Fontenay-aux-Roses, France; APHP, Service de Médecine Interne – Immunologie Clinique, Hôpitaux Universitaires Paris Sud, F-94270 Le Kremlin-Bicêtre, FranceUnité HIV, Inflammation et Persistance, Institut Pasteur, 25 rue du Dr. Roux, F-75025 Paris, FranceUnité HIV, Inflammation et Persistance, Institut Pasteur, 25 rue du Dr. Roux, F-75025 Paris, FranceDepartment of Biomedical Sciences, University of the Pacific, Arthur A. Dugoni School of Dentistry, 155 Fifth Street, San Francisco, CA 94103, USA; Université Paris Diderot, Sorbonne Paris Cité, 75013 Paris, FranceINSERM U1009, Gustave Roussy, 114 rue Edouard Vaillant, F-94805 Villejuif, FranceLaboratory of Molecular Radiotherapy, INSERM U1030, Gustave Roussy, 114 rue Edouard Vaillant, F-94805 Villejuif, France; Gustave Roussy, 114 rue Edouard Vaillant, F-94805 Villejuif, France; Université Paris Sud - Paris 11, 114 rue Edouard Vaillant, F-94805 Villejuif, FranceNational Institute for Infectious Diseases “Lazzaro Spallanzani,”, Via Portuense 292, 00149 Rome, Italy; Department of Biology, University of Rome “Tor Vergata,”, Via della Ricerca Scientifica 1, 00133 Rome, ItalyInstitut Pasteur, Antiviral Immunity, Biotherapy and Vaccine Unit, Infection and Epidemiology Department, 25 rue du Dr. Roux, F-75015 Paris, FranceINSERM U848, Gustave Roussy, 114 rue Edouard Vaillant, F-94805 Villejuif, France; Metabolomics Platform, Gustave Roussy, 114 rue Edouard Vaillant, Villejuif, France; Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, INSERM U1138, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Université Pierre et Marie Curie, Paris, France; Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France; Karolinska Institute, Department of Women’s and Children’s Health, Karolinska University Hospital, Stockholm, SwedenCell Death and Aging Team, Gustave Roussy, 114 rue Edouard Vaillant, F-94805 Villejuif, France; Laboratory of Molecular Radiotherapy, INSERM U1030, Gustave Roussy, 114 rue Edouard Vaillant, F-94805 Villejuif, France; Gustave Roussy, 114 rue Edouard Vaillant, F-94805 Villejuif, France; Université Paris Sud - Paris 11, 114 rue Edouard Vaillant, F-94805 Villejuif, France; Department of Biomedical Sciences, University of the Pacific, Arthur A. Dugoni School of Dentistry, 155 Fifth Street, San Francisco, CA 94103, USA; Corresponding authorSummary: Purinergic receptors and nucleotide-binding domain leucine-rich repeat containing (NLR) proteins have been shown to control viral infection. Here, we show that the NLR family member NLRP3 and the purinergic receptor P2Y2 constitutively interact and regulate susceptibility to HIV-1 infection. We found that NLRP3 acts as an inhibitory factor of viral entry that represses F-actin remodeling. The binding of the HIV-1 envelope to its host cell receptors (CD4, CXCR4, and/or CCR5) overcomes this restriction by stimulating P2Y2. Once activated, P2Y2 enhances its interaction with NLRP3 and stimulates the recruitment of the E3 ubiquitin ligase CBL to NLRP3, ultimately leading to NLRP3 degradation. NLRP3 degradation is permissive for PYK2 phosphorylation (PYK2Y402∗) and subsequent F-actin polymerization, which is required for the entry of HIV-1 into host cells. Taken together, our results uncover a mechanism by which HIV-1 overcomes NLRP3 restriction that appears essential for the accomplishment of the early steps of HIV-1 entry. : Paoletti et al. identified a constitutive interaction between NLRP3 and P2Y2 that regulates HIV-1 entry into target cells. They revealed that NLRP3 represses viral entry by impairing F-actin reorganization. HIV-1 overcomes this host cellular resistance by inducing NLRP3 degradation through the activation of P2Y2-dependent signaling pathway. Keywords: NLRP3, P2Y2, CBL, inflammasome, viral entry, HIVhttp://www.sciencedirect.com/science/article/pii/S2211124719302815 |
| spellingShingle | Audrey Paoletti Awatef Allouch Marina Caillet Hela Saïdi Frédéric Subra Roberta Nardacci Qiuji Wu Zeinaf Muradova Laurent Voisin Syed Qasim Raza Frédéric Law Maxime Thoreau Haithem Dakhli Olivier Delelis Béatrice Poirier-Beaudouin Nathalie Dereuddre-Bosquet Roger Le Grand Olivier Lambotte Asier Saez-Cirion Gianfranco Pancino David M. Ojcius Eric Solary Eric Deutsch Mauro Piacentini Marie-Lise Gougeon Guido Kroemer Jean-Luc Perfettini HIV-1 Envelope Overcomes NLRP3-Mediated Inhibition of F-Actin Polymerization for Viral Entry Cell Reports |
| title | HIV-1 Envelope Overcomes NLRP3-Mediated Inhibition of F-Actin Polymerization for Viral Entry |
| title_full | HIV-1 Envelope Overcomes NLRP3-Mediated Inhibition of F-Actin Polymerization for Viral Entry |
| title_fullStr | HIV-1 Envelope Overcomes NLRP3-Mediated Inhibition of F-Actin Polymerization for Viral Entry |
| title_full_unstemmed | HIV-1 Envelope Overcomes NLRP3-Mediated Inhibition of F-Actin Polymerization for Viral Entry |
| title_short | HIV-1 Envelope Overcomes NLRP3-Mediated Inhibition of F-Actin Polymerization for Viral Entry |
| title_sort | hiv 1 envelope overcomes nlrp3 mediated inhibition of f actin polymerization for viral entry |
| url | http://www.sciencedirect.com/science/article/pii/S2211124719302815 |
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