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. 2022 Jan 6;11:804976. doi: 10.3389/fcimb.2021.804976

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Copyright © 2022 De Angelis, Amatore, Checconi, Zevini, Fraternale, Magnani, Hiscott, De Chiara, Palamara and Nencioni

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Influenza virus infection affects the host antioxidant response. Schematic representation of the main redox-related pathways modulated by influenza virus infection. NRF2 protein is present at lower level into the nucleus of host infected cells, leading to a drop of the antioxidant gene expression, including G6PD. The reduction of SIRT2 expression affects the activation of G6PD enzyme that in turn leads to GSH/GSSG ratio decrease. Moreover, the infection induces oxidative stress condition also by increasing the NOX4-mediated ROS production. Finally, we observed that the rescue of NRF2 and G6PD expression impairs influenza virus replication. NOX4, nicotinamide adenine dinucleotide phosphate oxidase 4; ROS, reactive oxygen species; NRF2, nuclear factor erythroid 2-related factor 2; ARE, antioxidant response elements; G6PD, glucose-6-phosphate dehydrogenase; GSH, glutathione; GSSG, oxidized form of GSH; SIRT2, sirtuin 2; Ac K403, acetylated lysine 403; RNP, ribonucleoprotein.