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Mycobacterium tuberculosis reactivates HIV via exosomes mediated resetting of cellular redox potential and bioenergetics

Priyanka Tyagi, Virender Kumar Pal, Sandhya Srinivasan, View ORCID ProfileAmit Singh
doi: https://doi.org/10.1101/629048
Priyanka Tyagi
Department of Microbiology and Cell Biology, Centre for Infectious Disease, Research, Indian Institute of Science (IISc), Bangalore-12International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi-67
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Virender Kumar Pal
Department of Microbiology and Cell Biology, Centre for Infectious Disease, Research, Indian Institute of Science (IISc), Bangalore-12
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Sandhya Srinivasan
Vproteomics, New Delhi-16
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Amit Singh
Department of Microbiology and Cell Biology, Centre for Infectious Disease, Research, Indian Institute of Science (IISc), Bangalore-12
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  • ORCID record for Amit Singh
  • For correspondence: asingh@iisc.ac.in
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Abstract

The synergy between Mycobacterium tuberculosis (Mtb) and HIV-1 interferes with therapy and facilitates pathogenesis of both human pathogens. Fundamental mechanisms by which Mtb exacerbates HIV-1 are not clear. Here, we show that exosomes secreted by macrophages infected with Mtb, including drug-resistant clinical strains, reactivate HIV-1 by inducing oxidative stress. Mechanistically, Mtb-specific exosomes realign mitochondrial and non-mitochondrial oxygen consumption rate (OCR) and modulates the expression of genes mediating oxidative stress response, inflammation, and HIV-1 transactivation. Proteomics revealed the enrichment of several host factors (e.g., HIF-1α, galectins, Hsp90) known to promote HIV-1 reactivation in the Mtb-specific exosomes. Treatment with a known antioxidant, N-acetyl cysteine, or with the inhibitors of host factors galectins and Hsp90 attenuated HIV-1 reactivation by Mtb-specific exosomes. Our findings uncovered new paradigms for understanding the redox and bioenergetics basis of HIV-TB co-infection, which will enable the design of effective therapeutic strategies.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted May 07, 2019.
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Mycobacterium tuberculosis reactivates HIV via exosomes mediated resetting of cellular redox potential and bioenergetics
Priyanka Tyagi, Virender Kumar Pal, Sandhya Srinivasan, Amit Singh
bioRxiv 629048; doi: https://doi.org/10.1101/629048
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Mycobacterium tuberculosis reactivates HIV via exosomes mediated resetting of cellular redox potential and bioenergetics
Priyanka Tyagi, Virender Kumar Pal, Sandhya Srinivasan, Amit Singh
bioRxiv 629048; doi: https://doi.org/10.1101/629048

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