دورية أكاديمية
Bone degradation machinery of osteoclasts: An HIV-1 target that contributes to bone loss.
العنوان: | Bone degradation machinery of osteoclasts: An HIV-1 target that contributes to bone loss. |
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المؤلفون: | Raynaud-Messina B; Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, Université Paul Sabatier, 31400 Toulouse Cedex 4, France; raynaud@ipbs.fr maridono@ipbs.fr verollet@ipbs.fr.; International Associated Laboratory, CNRS 'Immuno-Metabolism-Macrophages-Tuberculosis/HIV' (1167), 31000 Toulouse, France.; International Associated Laboratory, CNRS 'Immuno-Metabolism-Macrophages-Tuberculosis/HIV' (1167), 1425 Buenos Aires, Argentina., Bracq L; INSERM U1016, Institut Cochin, 75014 Paris, France.; CNRS UMR8104, Université Paris Descartes, 75006 Paris, France.; Institut Pasteur Shanghai, Chinese Academy of Sciences, 200000 Shanghai, China., Dupont M; Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, Université Paul Sabatier, 31400 Toulouse Cedex 4, France.; International Associated Laboratory, CNRS 'Immuno-Metabolism-Macrophages-Tuberculosis/HIV' (1167), 31000 Toulouse, France.; International Associated Laboratory, CNRS 'Immuno-Metabolism-Macrophages-Tuberculosis/HIV' (1167), 1425 Buenos Aires, Argentina.; Institute of Experimental Medicine-Consejo Nacional de Investigaciones Científicas y Técnicas de Argentina, National Academy of Medicine, 1425 Buenos Aires, Argentina., Souriant S; Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, Université Paul Sabatier, 31400 Toulouse Cedex 4, France.; International Associated Laboratory, CNRS 'Immuno-Metabolism-Macrophages-Tuberculosis/HIV' (1167), 31000 Toulouse, France.; International Associated Laboratory, CNRS 'Immuno-Metabolism-Macrophages-Tuberculosis/HIV' (1167), 1425 Buenos Aires, Argentina., Usmani SM; Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Charlestown, MA 02129.; Harvard Medical School, Boston, MA 02115., Proag A; Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, Université Paul Sabatier, 31400 Toulouse Cedex 4, France., Pingris K; Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, Université Paul Sabatier, 31400 Toulouse Cedex 4, France.; International Associated Laboratory, CNRS 'Immuno-Metabolism-Macrophages-Tuberculosis/HIV' (1167), 31000 Toulouse, France.; International Associated Laboratory, CNRS 'Immuno-Metabolism-Macrophages-Tuberculosis/HIV' (1167), 1425 Buenos Aires, Argentina., Soldan V; Multiscale Electron Imaging Platform, 31062 Toulouse, France., Thibault C; Laboratory for Analysis and Architecture of Systems, CNRS, 31400 Toulouse, France.; Institut National des Sciences Appliquées de Toulouse, Université de Toulouse, 31400 Toulouse, France., Capilla F; INSERM, Université Paul Sabatier, École Nationale Vétérinaire de Toulouse, Centre Régional d'Exploration Fonctionnelle et de Ressources Expérimentales, Service d'Histopathologie, 31000 Toulouse Cedex 3, France., Al Saati T; INSERM, Université Paul Sabatier, École Nationale Vétérinaire de Toulouse, Centre Régional d'Exploration Fonctionnelle et de Ressources Expérimentales, Service d'Histopathologie, 31000 Toulouse Cedex 3, France., Gennero I; Centre de Physiopathologie de Toulouse-Purpan, INSERM-CNRS UMR 1043, Université Paul Sabatier, 31062 Toulouse, France.; Institut Fédératif de Biologie, Centre Hospitalier Universitaire Toulouse, 31059 Toulouse, France., Jurdic P; Institut de Génomique Fonctionnelle de Lyon, CNRS UMR3444, Université de Lyon, Ecole Normale Supérieure de Lyon, 69007 Lyon, France., Jolicoeur P; Division of Experimental Medicine, McGill University, Montreal, QC H3G 1A4, Canada.; Department of Microbiology and Immunology, University of Montreal, Montreal, QC H3T IJ4, Canada.; Laboratory of Molecular Biology, Clinical Research Institute of Montreal, Montreal, QC H2W 1R7, Canada., Davignon JL; INSERM, Université Paul Sabatier, École Nationale Vétérinaire de Toulouse, Centre Régional d'Exploration Fonctionnelle et de Ressources Expérimentales, Service d'Histopathologie, 31000 Toulouse Cedex 3, France.; Centre de Physiopathologie de Toulouse-Purpan, INSERM-CNRS UMR 1043, Université Paul Sabatier, 31062 Toulouse, France., Mempel TR; Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Charlestown, MA 02129.; Harvard Medical School, Boston, MA 02115., Benichou S; INSERM U1016, Institut Cochin, 75014 Paris, France.; CNRS UMR8104, Université Paris Descartes, 75006 Paris, France.; Institut Pasteur Shanghai, Chinese Academy of Sciences, 200000 Shanghai, China., Maridonneau-Parini I; Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, Université Paul Sabatier, 31400 Toulouse Cedex 4, France; raynaud@ipbs.fr maridono@ipbs.fr verollet@ipbs.fr.; International Associated Laboratory, CNRS 'Immuno-Metabolism-Macrophages-Tuberculosis/HIV' (1167), 31000 Toulouse, France.; International Associated Laboratory, CNRS 'Immuno-Metabolism-Macrophages-Tuberculosis/HIV' (1167), 1425 Buenos Aires, Argentina., Vérollet C; Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, Université Paul Sabatier, 31400 Toulouse Cedex 4, France; raynaud@ipbs.fr maridono@ipbs.fr verollet@ipbs.fr.; International Associated Laboratory, CNRS 'Immuno-Metabolism-Macrophages-Tuberculosis/HIV' (1167), 31000 Toulouse, France.; International Associated Laboratory, CNRS 'Immuno-Metabolism-Macrophages-Tuberculosis/HIV' (1167), 1425 Buenos Aires, Argentina. |
المصدر: | Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2018 Mar 13; Vol. 115 (11), pp. E2556-E2565. Date of Electronic Publication: 2018 Feb 20. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Washington, DC : National Academy of Sciences |
مواضيع طبية MeSH: | Bone Resorption/*etiology , HIV Infections/*complications , HIV-1/*physiology , Osteoclasts/*virology, Actins/metabolism ; Animals ; Bone Resorption/metabolism ; Bone Resorption/pathology ; Bone Resorption/physiopathology ; Bone and Bones/metabolism ; Cell Adhesion ; Female ; HIV Infections/metabolism ; HIV Infections/pathology ; HIV Infections/virology ; HIV-1/genetics ; Humans ; Mice ; Osteoclasts/cytology ; Osteoclasts/metabolism ; nef Gene Products, Human Immunodeficiency Virus/genetics ; nef Gene Products, Human Immunodeficiency Virus/metabolism |
مستخلص: | Bone deficits are frequent in HIV-1-infected patients. We report here that osteoclasts, the cells specialized in bone resorption, are infected by HIV-1 in vivo in humanized mice and ex vivo in human joint biopsies. In vitro, infection of human osteoclasts occurs at different stages of osteoclastogenesis via cell-free viruses and, more efficiently, by transfer from infected T cells. HIV-1 infection markedly enhances adhesion and osteolytic activity of human osteoclasts by modifying the structure and function of the sealing zone, the osteoclast-specific bone degradation machinery. Indeed, the sealing zone is broader due to F-actin enrichment of its basal units (i.e., the podosomes). The viral protein Nef is involved in all HIV-1-induced effects partly through the activation of Src, a regulator of podosomes and of their assembly as a sealing zone. Supporting these results, Nef-transgenic mice exhibit an increased osteoclast density and bone defects, and osteoclasts derived from these animals display high osteolytic activity. Altogether, our study evidences osteoclasts as host cells for HIV-1 and their pathological contribution to bone disorders induced by this virus, in part via Nef. Competing Interests: The authors declare no conflict of interest. |
التعليقات: | Comment in: Proc Natl Acad Sci U S A. 2018 Mar 13;115(11):2551-2553. (PMID: 29496959) |
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معلومات مُعتمدة: | R01 AI097052 United States AI NIAID NIH HHS; R01 DA036298 United States DA NIDA NIH HHS; Canada CIHR |
فهرسة مساهمة: | Keywords: HIV-1 infection; Nef; bone loss; osteoclast; podosome |
المشرفين على المادة: | 0 (Actins) 0 (nef Gene Products, Human Immunodeficiency Virus) 0 (nef protein, Human immunodeficiency virus 1) |
تواريخ الأحداث: | Date Created: 20180222 Date Completed: 20180919 Latest Revision: 20181113 |
رمز التحديث: | 20221213 |
مُعرف محوري في PubMed: | PMC5856515 |
DOI: | 10.1073/pnas.1713370115 |
PMID: | 29463701 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1091-6490 |
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DOI: | 10.1073/pnas.1713370115 |