Mycobacterium tuberculosis Reactivates HIV-1 via Exosome-Mediated Resetting of Cellular Redox Potential and Bioenergetics

MBio
P. TyagiAmit Singh

Abstract

The synergy between Mycobacterium tuberculosis and human immunodeficiency virus-1 (HIV-1) interferes with therapy and facilitates the pathogenesis of both human pathogens. Fundamental mechanisms by which M. tuberculosis exacerbates HIV-1 infection are not clear. Here, we show that exosomes secreted by macrophages infected with M. tuberculosis, including drug-resistant clinical strains, reactivated HIV-1 by inducing oxidative stress. Mechanistically, M. tuberculosis-specific exosomes realigned mitochondrial and nonmitochondrial oxygen consumption rates (OCR) and modulated the expression of host genes mediating oxidative stress response, inflammation, and HIV-1 transactivation. Proteomics analyses revealed the enrichment of several host factors (e.g., HIF-1α, galectins, and Hsp90) known to promote HIV-1 reactivation in M. tuberculosis-specific exosomes. Treatment with a known antioxidant-N-acetyl cysteine (NAC)-or with inhibitors of host factors-galectins and Hsp90-attenuated HIV-1 reactivation by M. tuberculosis-specific exosomes. Our findings uncover new paradigms for understanding the redox and bioenergetics bases of HIV-M. tuberculosis coinfection, which will enable the design of effective therapeutic strategies.IMPORTANCE Gl...Continue Reading

References

Dec 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·F J StaalL A Herzenberg
Jan 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·G PoliA S Fauci
Jan 1, 1995·American Journal of Respiratory and Critical Care Medicine·C WhalenJ Ellner
Mar 4, 1997·Proceedings of the National Academy of Sciences of the United States of America·L A HerzenbergL A Herzenberg
Apr 18, 1998·Proceedings of the National Academy of Sciences of the United States of America·J D PetersonC Waltenbaugh
Oct 13, 2000·European Journal of Clinical Investigation·S C De RosaL A Herzenberg
Oct 2, 2001·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Z ToossiC S Hirsch
Sep 19, 2002·The Journal of Biological Chemistry·Frederik VilhardtKarl-Heinz Krause
Jul 23, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·André BáficaAlan Sher
Jan 24, 2004·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Danyelle M TownsendHaim Tapiero
Feb 10, 2004·The Journal of Infectious Diseases·Delia GolettiEliana Coccia
Mar 23, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Henry C MwandumbaS Bertel Squire
Mar 15, 2006·The Journal of Cell Biology·Amy M BoothStephen J Gould
Apr 7, 2007·AIDS Research and Human Retroviruses·Annelie TjernlundBruce K Patterson
Aug 30, 2007·The Journal of Infectious Diseases·Charles D WellsKarin Weyer
Aug 11, 2007·American Journal of Respiratory and Critical Care Medicine·Kathryn DeRiemerCharles L Daley
May 13, 2008·Nature Methods·Marcus GutscherTobias P Dick
Sep 4, 2008·Biochemical and Biophysical Research Communications·Chul-Woong PyoSang-Yun Choi
Dec 9, 2008·The Biochemical Journal·Michael P Murphy
Jun 18, 2009·Current Opinion in Infectious Diseases·Sheela ShenoiGerald Friedland
Jun 23, 2009·Journal of Theoretical Biology·Libin Rong, Alan S Perelson
Sep 1, 2009·Biochemical and Biophysical Research Communications·Jong-Hyuk LeeHong-Duk Youn
Oct 3, 2009·American Journal of Respiratory and Critical Care Medicine·Barbara KalsdorfRobert J Wilkinson
Oct 10, 2009·Molecular & Cellular Proteomics : MCP·Bai-Yu LeeMarcus A Horwitz
Nov 12, 2009·The Journal of Biological Chemistry·Kazuhiro NakamuraGary L Johnson
Jan 26, 2010·Expert Reviews in Molecular Medicine·John S Albin, Reuben S Harris
May 14, 2010·Journal of Virology·Holly A SadlerLouis M Mansky

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Methods Mentioned

BETA
biosensor
flow cytometry
PMA
PCR
transmission electron microscopy
enzyme-linked immunosorbent assay
ELISA
bronchoalveolar lavage
density gradient centrifugation

Software Mentioned

ProstaR
Sequest HT
NanoString
GraphPad Prism
nSolver
- clusterProfiler
NanoString nCounter
R package
Wave Desktop
Sequest

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