TY - JOUR T1 - Mycobacterium tuberculosis reactivates HIV via exosomes mediated resetting of cellular redox potential and bioenergetics JF - bioRxiv DO - 10.1101/629048 SP - 629048 AU - Priyanka Tyagi AU - Virender Kumar Pal AU - Sandhya Srinivasan AU - Amit Singh Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/05/07/629048.abstract N2 - 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. ER -