Antioxidant nanozyme counteracts HIV‐1 by modulating intracellular redox potential

• Published in: EMBO molecular medicine Vol. 13; no. 5; pp. e13314 - n/a
• Main Authors: Singh, Shalini, Ghosh, Sourav, Pal, Virender Kumar, Munshi, MohamedHusen, Shekar, Pooja, Narasimha Murthy, Diwakar Tumkur, Mugesh, Govindasamy, Singh, Amit
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 07.05.2021; EMBO Press; John Wiley and Sons Inc; Springer Nature
• Subjects: Antioxidants; Antiretroviral drugs; Antiretroviral therapy; Apoptosis; CD4 antigen; EMBO08; EMBO23; Enzymes; Genomes; Glutathione; Glutathione peroxidase; HIV; Human immunodeficiency virus; Hydrogen peroxide; Immune system; Infections; Infectious diseases; latency; Latent infection; Lymphocytes T; Metabolism; Nanomaterials; Nanoparticles; Nanowires; nanozymes; Oxidative stress; Reactive oxygen species; Redox potential; Replication; Scanning electron microscopy; Spectrum analysis; Vanadium; Vanadium pentoxide; nanozymes; HIV; glutathione; latency; glutathione peroxidase
• ISSN: 1757-4676; 1757-4684; 1757-4684
• DOI: 10.15252/emmm.202013314

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 (V 2 O 5 ) 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 V 2 O 5 nanosheets catalyze ROS neutralization in HIV‐1‐infected cells and uniformly block viral reactivation and replication. Mechanistically, V 2 O 5 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 V 2 O 5 nanosheets with a pharmacological inhibitor of NF‐κB (BAY11‐7082) abrogated reactivation of HIV‐1. Lastly, V 2 O 5 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 V 2 O 5 nanosheets against HIV and suggested nanozymes as future platforms to develop interventions against infectious diseases. Synopsis This study describes a vanadium pentoxide (V 2 O 5 )‐based nanozyme that bolsters the anti‐HIV potential of immune cells and suppresses viral rebound in latently infected CD4 + T cells derived from HIV subjects. Ultrathin sheets of V 2 O 5 ‐based nanozyme (Vs) exhibited efficient glutathione peroxidase activity inside the HIV infected cells. Vs suppressed HIV reactivation in cell line models of latency and in latently infected human CD4 + T cells. Vs inhibited HIV replication in primary CD4 + T cells and macrophages. Vs altered the expression of genes involved in the antioxidant response, HIV transcription, and apoptosis. Vs combined with antiretrovirals could be explored for delaying viral rebound, replication, and reseeding of reservoirs. Graphical Abstract This study describes a vanadium pentoxide (V 2 O 5 )‐based nanozyme that bolsters the anti‐HIV potential of immune cells and suppresses viral rebound in latently infected CD4 + T cells derived from HIV subjects.