دورية أكاديمية
أعرض في EDS

An Asymmetric Opening of HIV-1 Envelope Mediates Antibody-Dependent Cellular Cytotoxicity.

التفاصيل البيبلوغرافية
العنوان: An Asymmetric Opening of HIV-1 Envelope Mediates Antibody-Dependent Cellular Cytotoxicity.
المؤلفون: Alsahafi N; Centre de Recherche du CHUM, Montreal, QC, Canada; Department of Microbiology and Immunology, McGill University, Montreal, QC, Canada., Bakouche N; Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA, USA., Kazemi M; Department of Biochemistry and Molecular Biology and Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC, Australia., Richard J; Centre de Recherche du CHUM, Montreal, QC, Canada; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC, Canada., Ding S; Centre de Recherche du CHUM, Montreal, QC, Canada; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC, Canada., Bhattacharyya S; Department of Biochemistry and Molecular Biology and Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC, Australia., Das D; Department of Biochemistry and Molecular Biology and Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC, Australia., Anand SP; Centre de Recherche du CHUM, Montreal, QC, Canada; Department of Microbiology and Immunology, McGill University, Montreal, QC, Canada., Prévost J; Centre de Recherche du CHUM, Montreal, QC, Canada; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC, Canada., Tolbert WD; Infectious Diseases Division, Uniformed Services University of the Health Sciences, Bethesda, MD, USA., Lu H; Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, New York, NY, USA., Medjahed H; Centre de Recherche du CHUM, Montreal, QC, Canada., Gendron-Lepage G; Centre de Recherche du CHUM, Montreal, QC, Canada., Ortega Delgado GG; Centre de Recherche du CHUM, Montreal, QC, Canada., Kirk S; Department of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104-6323, USA., Melillo B; Department of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104-6323, USA., Mothes W; Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536, USA., Sodroski J; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA., Smith AB 3rd; Department of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104-6323, USA., Kaufmann DE; Centre de Recherche du CHUM, Montreal, QC, Canada; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC, Canada; Department of Medicine, Université de Montréal, Montreal, QC, Canada; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA., Wu X; Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, New York, NY, USA., Pazgier M; Infectious Diseases Division, Uniformed Services University of the Health Sciences, Bethesda, MD, USA., Rouiller I; Department of Biochemistry and Molecular Biology and Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC, Australia. Electronic address: isabelle.rouiller@unimelb.edu.au., Finzi A; Centre de Recherche du CHUM, Montreal, QC, Canada; Department of Microbiology and Immunology, McGill University, Montreal, QC, Canada; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC, Canada. Electronic address: andres.finzi@umontreal.ca., Munro JB; Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA, USA. Electronic address: james.munro@tufts.edu.
المصدر: Cell host & microbe [Cell Host Microbe] 2019 Apr 10; Vol. 25 (4), pp. 578-587.e5.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Cell Press Country of Publication: United States NLM ID: 101302316 Publication Model: Print Cited Medium: Internet ISSN: 1934-6069 (Electronic) Linking ISSN: 19313128 NLM ISO Abbreviation: Cell Host Microbe Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Cambridge, Mass. : Cell Press
مواضيع طبية MeSH: Antibody-Dependent Cell Cytotoxicity*, CD4-Positive T-Lymphocytes/*virology , HIV Antibodies/*immunology , HIV-1/*immunology , env Gene Products, Human Immunodeficiency Virus/*immunology, CD4 Antigens/metabolism ; Cells, Cultured ; Humans ; Protein Binding ; Protein Conformation ; env Gene Products, Human Immunodeficiency Virus/chemistry
مستخلص: The HIV-1 envelope glycoprotein (Env) (gp120-gp41) 3 is the target for neutralizing antibodies and antibody-dependent cellular cytotoxicity (ADCC). HIV-1 Env is flexible, sampling different conformational states. Before engaging CD4, Env adopts a closed conformation (State 1) that is largely antibody resistant. CD4 binding induces an intermediate state (State 2), followed by an open conformation (State 3) that is susceptible to engagement by antibodies that recognize otherwise occluded epitopes. We investigate conformational changes in Env that induce ADCC in the presence of a small-molecule CD4-mimetic compound (CD4mc). We uncover an asymmetric Env conformation (State 2A) recognized by antibodies targeting the conserved gp120 inner domain and mediating ADCC. Sera from HIV+ individuals contain these antibodies, which can stabilize Env State 2A in combination with CD4mc. Additionally, triggering State 2A on HIV-infected primary CD4 + T cells exposes epitopes that induce ADCC. Strategies that induce this Env conformation may represent approaches to fight HIV-1 infection.
(Copyright © 2019 Elsevier Inc. All rights reserved.)
التعليقات: Comment in: Cell Host Microbe. 2019 Jun 12;25(6):767-768. doi: 10.1016/j.chom.2019.05.009. (PMID: 31194935)
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معلومات مُعتمدة: UM1 AI100663 United States AI NIAID NIH HHS; R01 AI129769 United States AI NIAID NIH HHS; P01 GM056550 United States GM NIGMS NIH HHS; HHSN261200800001C United States CA NCI NIH HHS; R01 AI124982 United States AI NIAID NIH HHS; R01 AI122953 United States AI NIAID NIH HHS; R01 AI116274 United States AI NIAID NIH HHS; HHSN261200800001E United States CA NCI NIH HHS; K22 AI116262 United States AI NIAID NIH HHS
فهرسة مساهمة: Keywords: 17b; A32; ADCC; CD4i Abs; HIV-1; State 2A; cryo-EM; envelope glycoproteins; smFRET
المشرفين على المادة: 0 (CD4 Antigens)
0 (HIV Antibodies)
0 (env Gene Products, Human Immunodeficiency Virus)
تواريخ الأحداث: Date Created: 20190412 Date Completed: 20191121 Latest Revision: 20240615
رمز التحديث: 20240615
مُعرف محوري في PubMed: PMC6592637
DOI: 10.1016/j.chom.2019.03.002
PMID: 30974085
قاعدة البيانات: MEDLINE
الوصف
تدمد:1934-6069
DOI:10.1016/j.chom.2019.03.002