PMID:
mBio. 2020 Mar 3 ;11(2). Epub 2020 Mar 3. PMID: 32127457
Abstract Title:
Mycobacterium tuberculosis Reactivates HIV-1 via Exosome-Mediated Resetting of Cellular Redox Potential and Bioenergetics.
Abstract:
The synergy betweenand human immunodeficiency virus-1 (HIV-1) interferes with therapy and facilitates the pathogenesis of both human pathogens. Fundamental mechanisms by whichexacerbates HIV-1 infection are not clear. Here, we show that exosomes secreted by macrophages infected with, including drug-resistant clinical strains, reactivated HIV-1 by inducing oxidative stress. Mechanistically,-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-specific exosomes. Treatment with a known antioxidant-N-acetyl cysteine (NAC)-or with inhibitors of host factors-galectins and Hsp90-attenuated HIV-1 reactivation byspecific exosomes. Our findings uncover new paradigms for understanding the redox and bioenergetics bases of HIV-coinfection, which will enable the design of effective therapeutic strategies.Globally, individuals coinfected with the AIDS virus (HIV-1) and with(causative agent of tuberculosis [TB]) pose major obstacles in the clinical management of both diseases. At the heart of this issue is the apparent synergy between the two human pathogens. On the one hand, mechanisms induced by HIV-1 for reactivation of TB in AIDS patients are well characterized. On the other hand, while clinical findings clearly identified TB as a risk factor for HIV-1 reactivation and associated mortality, basic mechanisms by whichexacerbates HIV-1 replication and infection remain poorly characterized. The significance of our research is in identifying the role of fundamental mechanisms such as redox and energy metabolism in catalyzing HIV-synergy. The quantification of redox and respiratory parameters affected byin stimulating HIV-1 will greatly enhance our understanding of HIV-coinfection, leading to a wider impact on the biomedical research community and creating new translational opportunities.
Health Time 