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Antioxidant nanozyme counteracts HIV-1 by modulating intracellular redox potential.


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 (V2 O5 ) 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 V2 O5 nanosheets catalyze ROS neutralization in HIV-1-infected cells and uniformly block viral reactivation and replication. Mechanistically, V2 O5 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 V2 O5 nanosheets with a pharmacological inhibitor of NF-κB (BAY11-7082) abrogated reactivation of HIV-1. Lastly, V2 O5 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 V2 O5 nanosheets against HIV and suggested nanozymes as future platforms to develop interventions against infectious diseases.

SUBMITTER: Singh S 

PROVIDER: S-EPMC8103102 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Antioxidant nanozyme counteracts HIV-1 by modulating intracellular redox potential.

Singh Shalini S   Ghosh Sourav S   Pal Virender Kumar VK   Munshi MohamedHusen M   Shekar Pooja P   Narasimha Murthy Diwakar Tumkur DT   Mugesh Govindasamy G   Singh Amit A  

EMBO molecular medicine 20210401 5


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<sub>2</sub> O<sub>5</sub> ) nanosheets functionally mimic natural glutathione peroxidase activity to mitigate ROS associated with HIV-1 infection without adversely affe  ...[more]

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