Antioxidant nanozyme counteracts HIV-1 by modulating intracellular redox potential

Singh, S and Ghosh, S and Pal, VK and Munshi, M and Shekar, P and Narasimha Murthy, DT and Mugesh, G and Singh, A (2021) Antioxidant nanozyme counteracts HIV-1 by modulating intracellular redox potential. In: EMBO Molecular Medicine .

Preview	PDF emb_mol_med_13-05_2021.pdf - Published Version Download (2MB) | Preview
Preview	PDF emmm202013314-sup-0002-evfigs.pdf - Published Supplemental Material Download (806kB) | Preview
Preview	PDF emmm202013314-sup-0001-appendix.pdf - Published Supplemental Material Download (989kB) | Preview
	Archive (ZIP) emmm202013314-sup-0004-sdataev.zip - Published Supplemental Material Download (350kB)

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. ©2021 The Authors. Published under the terms of the CC BY 4.0 license

Item Type:	Journal Article
Publication:	EMBO Molecular Medicine
Publisher:	Blackwell Publishing Ltd
Additional Information:	The copyright for this article belongs to Authors
Department/Centre:	Division of Biological Sciences > Microbiology & Cell Biology Division of Biological Sciences > Centre for Infectious Disease Research Division of Chemical Sciences > Inorganic & Physical Chemistry
Date Deposited:	12 Jul 2021 07:41
Last Modified:	12 Jul 2021 07:41
URI:	http://eprints.iisc.ac.in/id/eprint/68829

Actions (login required)

View Item