title: Syncytial apoptosis signaling network induced by the HIV-1 envelope glycoprotein complex: an overview.
abstract: Infection by human immunodeficiency virus-1 (HIV-1) is associated with a progressive decrease in CD4 T-cell numbers and the consequent collapse of host immune defenses. The major pathogenic mechanism of AIDS is the massive apoptotic destruction of the immunocompetent cells, including uninfected cells. The latter process, also known as by-stander killing, operates by various mechanisms one of which involves the formation of syncytia which undergo cell death by following a complex pathway. We present here a detailed and curated map of the syncytial apoptosis signaling network, aimed at simplifying the whole mechanism that we have characterized at the molecular level in the last 15 years. The map was created using Systems Biology Graphical Notation language with the help of CellDesigner software and encompasses 36 components (proteins/genes) and 54 interactions. The simplification of this complex network paves the way for the development of novel therapeutic strategies to eradicate HIV-1 infection. Agents that induce the selective death of HIV-1-elicited syncytia might lead to the elimination of viral reservoirs and hence constitute an important complement to current antiretroviral therapies.
authors.affiliation: Laboratory of Cell Biology and Electron Microscopy, National Institute for Infectious Diseases, IRCCS 'L. Spallanzani', Rome, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Nardacci
authors.affiliation: 1] Cell Death and Aging Team, Gustave Roussy, Villejuif, France [2] Laboratory of Molecular Radiotherapy, INSERM U1030, Gustave Roussy, Villejuif, France [3] Gustave Roussy, Villejuif, France [4] Université Paris Sud-Paris 11, Villejuif, France.
authors.forename: J-L
authors.initials: JL
authors.lastname: Perfettini
authors.affiliation: 1] Aix-Marseille Université, Marseille, France [2] TAGC-Inserm U1090, Marseille, France [3] Institut de Biologie de l'Ecole Normale Supérieure (IBENS), Paris, France [4] UMR 8197 Centre National de la Recherche Scientifique (CNRS), Paris, France [5] INSERM U1024, Paris, France [6] Institut Curie, Paris, France [7] Clinical Operational Research Unit, University College London, London, UK.
authors.forename: L
authors.initials: L
authors.lastname: Grieco
authors.affiliation: 1] Aix-Marseille Université, Marseille, France [2] TAGC-Inserm U1090, Marseille, France [3] Institut de Biologie de l'Ecole Normale Supérieure (IBENS), Paris, France [4] UMR 8197 Centre National de la Recherche Scientifique (CNRS), Paris, France [5] INSERM U1024, Paris, France [6] INRIA Paris-Rocquencourt, Rocquencourt, France.
authors.forename: D
authors.initials: D
authors.lastname: Thieffry
authors.affiliation: 1] Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, Paris, France [2] Université Paris Descartes/Paris V; Sorbonne Paris Cité, Paris, France [3] INSERM,U1138, Villejuif, France [4] Metabolomics and Cell Biology Platforms, Gustave Roussy, Villejuif, France [5] Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.
authors.forename: G
authors.initials: G
authors.lastname: Kroemer
authors.affiliation: 1] Laboratory of Cell Biology and Electron Microscopy, National Institute for Infectious Diseases, IRCCS 'L. Spallanzani', Rome, Italy [2] Department of Biology, University of Rome 'Tor Vergata', Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Piacentini
mesh_terms: D017209:Apoptosis / Q000235:genetics; D024201:Bystander Effect / Q000235:genetics; D015704:CD4 Antigens / Q000235:genetics / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D002459:Cell Fusion; D005786:Gene Expression Regulation; D015726:Giant Cells / Q000378:metabolism* / Q000473:pathology; D019302:HIV Envelope Protein gp160 / Q000235:genetics / Q000378:metabolism*; D015658:HIV Infections / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D054884:Host-Pathogen Interactions / Q000235:genetics; D006801:Humans; D025941:Protein Interaction Mapping; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D011983:Receptors, Purinergic / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*
chemical_list: D015704:CD4 Antigens; C527276:CXCR4 protein, human; D019302:HIV Envelope Protein gp160; D019718:Receptors, CXCR4; D011983:Receptors, Purinergic