دورية أكاديمية

Alterations of redox and iron metabolism accompany the development of HIV latency.

التفاصيل البيبلوغرافية
العنوان: Alterations of redox and iron metabolism accompany the development of HIV latency.
المؤلفون: Shytaj IL; Heidelberg University Hospital, Heidelberg, Germany.; German Center for Infection Research, Heidelberg, Germany., Lucic B; Heidelberg University Hospital, Heidelberg, Germany.; German Center for Infection Research, Heidelberg, Germany., Forcato M; Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy., Penzo C; Heidelberg University Hospital, Heidelberg, Germany., Billingsley J; Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA., Laketa V; Heidelberg University Hospital, Heidelberg, Germany.; German Center for Infection Research, Heidelberg, Germany., Bosinger S; Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.; Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA., Stanic M; Heidelberg University Hospital, Heidelberg, Germany., Gregoretti F; Institute for High Performance Computing and Networking, ICAR-CNR, Naples, Italy., Antonelli L; Institute for High Performance Computing and Networking, ICAR-CNR, Naples, Italy., Oliva G; Institute for High Performance Computing and Networking, ICAR-CNR, Naples, Italy., Frese CK; CECAD Research Center, University of Cologne, Cologne, Germany., Trifunovic A; CECAD Research Center, University of Cologne, Cologne, Germany., Galy B; Division of Virus-Associated Carcinogenesis, German Cancer Research Centre, Heidelberg, Germany., Eibl C; Leibniz-Forschungsinstitut für Molekulare Pharmakologie, Berlin, Germany.; Institute of Biology, Cellular Biophysics, Humboldt Universität zu Berlin, Berlin, Germany., Silvestri G; Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.; Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA., Bicciato S; Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy., Savarino A; Italian Institute of Health, Rome, Italy., Lusic M; Heidelberg University Hospital, Heidelberg, Germany.; German Center for Infection Research, Heidelberg, Germany.
المصدر: The EMBO journal [EMBO J] 2020 May 04; Vol. 39 (9), pp. e102209. Date of Electronic Publication: 2020 Mar 11.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 8208664 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1460-2075 (Electronic) Linking ISSN: 02614189 NLM ISO Abbreviation: EMBO J Subsets: MEDLINE
أسماء مطبوعة: Publication: 2024- : [London] : Nature Publishing Group
Original Publication: Eynsham, Oxford, England : Published for the European Molecular Biology Organization by IRL Press, [c1982-
مواضيع طبية MeSH: Gene Regulatory Networks*, HIV Infections/*virology , HIV-1/*physiology , Iron/*metabolism , Promyelocytic Leukemia Protein/*metabolism, Animals ; Cell Line ; Disease Models, Animal ; HIV Infections/genetics ; HIV Infections/metabolism ; Humans ; Macaca ; Oxidation-Reduction ; Proteolysis ; Sequence Analysis, RNA ; Sumoylation ; Up-Regulation ; Virus Latency
مستخلص: HIV-1 persists in a latent form during antiretroviral therapy, mainly in CD4 + T cells, thus hampering efforts for a cure. HIV-1 infection is accompanied by metabolic alterations, such as oxidative stress, but the effect of cellular antioxidant responses on viral replication and latency is unknown. Here, we show that cells survive retroviral replication, both in vitro and in vivo in SIVmac-infected macaques, by upregulating antioxidant pathways and the intertwined iron import pathway. These changes are associated with remodeling of promyelocytic leukemia protein nuclear bodies (PML NBs), an important constituent of nuclear architecture and a marker of HIV-1 latency. We found that PML NBs are hyper-SUMOylated and that PML protein is degraded via the ubiquitin-proteasome pathway in productively infected cells, before latency establishment and after reactivation. Conversely, normal numbers of PML NBs were restored upon transition to latency or by decreasing oxidative stress or iron content. Our results highlight antioxidant and iron import pathways as determinants of HIV-1 latency and support their pharmacologic inhibition as tools to regulate PML stability and impair latency establishment.
(© 2020 The Authors. Published under the terms of the CC BY 4.0 license.)
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معلومات مُعتمدة: 04.704 International Deutsches Zentrum für Infektionsforschung (DZIF); 04.810 International Deutsches Zentrum für Infektionsforschung (DZIF); International Gilead Sciences (Gilead); International Humboldt Foundation
فهرسة مساهمة: Keywords: HIV-1 latency; iron; oxidative stress; promyelocytic leukemia protein; proteasome
سلسلة جزيئية: GEO GSE127468; GSE73232
PDB 5yuf
المشرفين على المادة: 0 (Promyelocytic Leukemia Protein)
143220-95-5 (PML protein, human)
E1UOL152H7 (Iron)
تواريخ الأحداث: Date Created: 20200312 Date Completed: 20201211 Latest Revision: 20231113
رمز التحديث: 20231113
مُعرف محوري في PubMed: PMC7196916
DOI: 10.15252/embj.2019102209
PMID: 32157726
قاعدة البيانات: MEDLINE
الوصف
تدمد:1460-2075
DOI:10.15252/embj.2019102209