Antioxidant nanozyme counteracts HIV‐1 by modulating intracellular redox potential

Shalini Singh,Amit Singh,Diwakar Tumkur Narasimha Murthy,Govindasamy Mugesh,Virender Kumar Pal,Mohamedhusen Munshi,Pooja Shekar,Sourav Ghosh

doi:10.15252/emmm.202013314

Abstract

Reactive oxygen species (ROS) regulates the replication of human immunodeficiency virus (HIV‐1) during infection. However, the application of this knowledge to develop therapeutic strategies remained unsuccessful due to the harmful consequences of manipulating cellular antioxidant systems. Here, we show that vanadium pentoxide (V2O5) nanosheets functionally mimic natural glutathione peroxidase activity to mitigate ROS associated with HIV‐1 infection without adversely affecting cellular physiology. Using genetic reporters of glutathione redox potential and hydrogen peroxide, we showed that V2O5 nanosheets catalyze ROS neutralization in HIV‐1‐infected cells and uniformly block viral reactivation and replication. Mechanistically, V2O5 nanosheets suppressed HIV‐1 by affecting the expression of pathways coordinating redox balance, virus transactivation (e.g., NF‐κB), inflammation, and apoptosis. Importantly, a combination of V2O5 nanosheets with a pharmacological inhibitor of NF‐κB (BAY11‐7082) abrogated reactivation of HIV‐1. Lastly, V2O5 nanosheets inhibit viral reactivation upon prostratin stimulation of latently infected CD4+ T cells from HIV‐infected patients receiving suppressive antiretroviral therapy. Our data successfully revealed the usefulness of V2O5 nanosheets against HIV and suggested nanozymes as future platforms to develop interventions against infectious diseases.

Highlights

C Full width half maxima (FWHM) and binding energies of deconvoluted oxygen and vanadium XPS peaks
A Recycling activity of Vs during multiple rounds of catalysis was analyzed by addition of fresh substrates in the reaction mixture up to six cycles
Conditions used for the assay were sodium phosphate buffer (100 mM, pH 7.4), GSH (2 mM), NADPH (0.2 mM), catalyst (20 ng/ll), GR (~1.7 U), and H2O2 (20 lM) at 25°C

Summary

Introduction

C Full width half maxima (FWHM) and binding energies of deconvoluted oxygen and vanadium XPS peaks. A Recycling activity of Vs during multiple rounds of catalysis was analyzed by addition of fresh substrates in the reaction mixture up to six cycles. The curves observed due to reduction in NADPH absorbance, for every cycle were parallel to each other, indicating no change in their initial rate and persistence of the activity. Conditions used for the assay were sodium phosphate buffer (100 mM, pH 7.4), GSH (2 mM), NADPH (0.2 mM), catalyst (20 ng/ll), GR (~1.7 U), and H2O2 (20 lM) at 25°C.

Results

Conclusion