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

The EMBO Journal
Iart Luca ShytajMarina Lusic

Abstract

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.

References

Oct 1, 1995·Free Radical Biology & Medicine·G W Pace, C D Leaf
Jun 1, 1994·Chemico-biological Interactions·J Piette, S Legrand-Poels
Nov 1, 1993·The Journal of Experimental Medicine·M WoodrowD Cantrell
Jul 22, 1998·Proceedings of the National Academy of Sciences of the United States of America·T W ChunA S Fauci
Nov 30, 1999·Nature·T W ChunA S Fauci
Feb 13, 2001·Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology·B S van AsbeckJ J Marx
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Nov 30, 2004·Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology·Hafsatou Ndama Traoré, Debra Meyer
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aravind SubramanianJill P Mesirov
Jun 17, 2006·Cancer Research·Wilfried CondemineHugues de Thé
Jul 17, 2007·Virology·Zufan DebebeSergei Nekhai
Jul 24, 2007·Cytokine·Samuel A Williams, Warner C Greene
Jan 1, 1993·IEEE Transactions on Image Processing : a Publication of the IEEE Signal Processing Society·L Vincent
Jun 17, 2008·Nature Reviews. Microbiology·Hal Drakesmith, Andrew Prentice
Oct 14, 2008·Blood·Alberto Bosque, Vicente Planelles
Mar 11, 2009·Frontiers in Bioscience (Landmark Edition)·Dora TorokDavid P Bazett-Jones
May 5, 2009·Free Radical Biology & Medicine·Hong-Sheng ZhangHong-Sen Zhou
Jun 23, 2009·Nature Medicine·Nicolas ChomontRafick-Pierre Sékaly
Jan 9, 2010·Annual Review of Pharmacology and Toxicology·Raffaella GozzelinoMiguel P Soares
Jan 9, 2010·Acta Crystallographica. Section D, Biological Crystallography·Vincent B ChenDavid C Richardson
Apr 13, 2010·Acta Crystallographica. Section D, Biological Crystallography·P EmsleyK Cowtan
Nov 12, 2010·BMC Research Notes·Keiko SuzukiKarl Riabowol
Dec 4, 2010·Retrovirology·Min XuSergei Nekhai
May 7, 2011·Bioinformatics·Arthur LiberzonJill P Mesirov
Jan 10, 2012·Cold Spring Harbor Perspectives in Medicine·Robert F Siliciano, Warner C Greene
Jun 30, 2012·Nature Methods·Johannes SchindelinAlbert Cardona
Oct 30, 2012·Bioinformatics·Alexander DobinThomas R Gingeras
Nov 14, 2012·The Journal of Cell Biology·Alfred L Goldberg
Jan 9, 2013·Annual Review of Pharmacology and Toxicology·Qiang Ma
Mar 19, 2013·Nature Structural & Molecular Biology·Janina BeckerFrauke Melchior
Apr 26, 2013·Current Opinion in HIV and AIDS·David T Evans, Guido Silvestri
Jun 19, 2013·Cell Host & Microbe·Marina LusicMauro Giacca
Aug 10, 2013·Nature Protocols·Daniela GiustariniRanieri Rossi
Nov 30, 2013·Nature Reviews. Drug Discovery·Chiara GorriniTak W Mak
Mar 19, 2014·The Journal of Cell Biology·Umut SahinValérie Lallemand-Breitenbach
Aug 28, 2014·The Journal of Biological Chemistry·James A Imlay
Sep 10, 2014·The Journal of Clinical Investigation·Alexander J GillDennis L Kolson
Oct 8, 2014·AIDS Research and Human Retroviruses·Hsiang-Chun ChangHossein Ardehali
Nov 20, 2014·The Journal of Biological Chemistry·Ashima BhaskarAmit Singh

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Citations

Apr 25, 2020·Viruses·Nabab KhanJonathan D Geiger
Feb 10, 2021·Viruses·Antonio Victor Campos CoelhoLucas André Cavalcanti Brandão
Apr 2, 2021·EMBO Molecular Medicine·Shalini SinghAmit Singh
Apr 11, 2021·Proceedings of the National Academy of Sciences of the United States of America·Yiyang LuRoy D Dar
May 25, 2021·Frontiers in Cellular and Infection Microbiology·J Peter Svensson
Mar 24, 2021·Cold Spring Harbor Perspectives in Biology·Bojana LucicMarina Lusic
Mar 25, 2021·Journal of Molecular Cell Biology·Viviana Scoca, Francesca Di Nunzio

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Datasets Mentioned

BETA
GSE127468
GSE73232

Methods Mentioned

BETA
flow cytometry
PCR
proteomic profiling
nuclear translocation
confocal microscopy
ubiquitination
Assay
FCS
FACS
Protein Assay

Clinical Trials Mentioned

NCT03980665

Software Mentioned

FlowJo
Imspector
Biocarta
STAR
fspecial MATLAB
GraphPad Prism
01
GraphPad
Gene Set Enrichment Analysis ( GSEA )
PyMOL

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