Redox control in the pathophysiology of influenza virus infection

Abstract

Triggered in response to external and internal ligands in cells and animals, redox homeostasis is transmitted via signal molecules involved in defense redox mechanisms through networks of cell proliferation, differentiation, intracellular detoxification, bacterial infection, and immune reactions. Cellular oxidation is not necessarily harmful per se, but its effects depend on the balance between the peroxidation and antioxidation cascades, which can vary according to the stimulus and serve to maintain oxygen homeostasis. The reactive oxygen species (ROS) that are generated during influenza virus (IV) infection have critical effects on both the virus and host cells. In this review, we outline the link between viral infection and redox control using IV infection as an example. We discuss the current state of knowledge on the molecular relationship between cellular oxidation mediated by ROS accumulation and the diversity of IV infection. We also summarize the potential anti-IV agents available currently that act by targeting redox biology/pathophysiology.

Nrf2-interacting nutrients and COVID-19: time for research to develop adaptation strategies

“…One of the key features of the complex interaction between nutrients and the oxidative stress/inflammatory response is the differential regulation of NFκB and Nrf2 by the cell redox status [118 ]. Nrf2 and NFκb are present in an inactive form in the cytosol since they are linked to an inhibitory compound iNFκB or INrf2 (Keap 1), both targets of reactive oxygen species [119–121 ]. In the case of a large production of ROS, which would overwhelm the antioxidant defence, iNFκB is oxidized and catabolized.…”

“…Once produced, cytokines are able to activate oxidant production by the NADPH oxidase complex, leading to an oxidative burst, which could in turn enhance NFκB activation. Thus, NFκB activation results in a directional and synergistic linkage of inflammation and oxidative stress [ 120 , 124 ].…”

G6PD deficiency, redox homeostasis, and viral infections: implications for SARS-CoV-2 (COVID-19)

“…The immune responses are closely associated with the redox balance. The redox milieu can modulate viral replication, including HIV, influenza, and respiratory syncytial viruses [44][45][46]. Antioxidant therapy may prove effective in the prevention of viral infection through redox control [47][48][49][50], while insufficient antioxidant capacity is conducive to viral production and virulence [51,52].…”

Perspectives on mechanistic implications of ROS inducers for targeting viral infections

“…Maintenance of a delicate oxidant-antioxidant balance is imperative for the promotion of viral replication, protection of viral genetic material and host cell from excessive oxidative damage and restraining the antiviral immune responses ( Lee, 2018b ; Reshi et al, 2014 ). Thus, tipping oxidant-antioxidant balance using pharmacological agents towards antioxidant state should promote viral replication and if shifted toward pro-oxidant state should result in enhanced oxidative stress and inhibition of the viral replication ( Chen et al, 2020a ; Lee, 2018b ; Nakamura et al, 2010 ). Hence, the administration of antioxidants like Vitamin C, which has been proved to be preventive against viral pneumonia, can serve as an ideal prevention strategy against viral infections; however, ROS induction can be superlative in disease therapy ( Hemilä and Louhiala, 2013 ; Kim et al, 2013 ).…”

“…Hence, the administration of antioxidants like Vitamin C, which has been proved to be preventive against viral pneumonia, can serve as an ideal prevention strategy against viral infections; however, ROS induction can be superlative in disease therapy ( Hemilä and Louhiala, 2013 ; Kim et al, 2013 ). Further, there are several host redox and other associated genes which are modulated during a viral infection enabling the viral propagation and pathogenesis as depicted in Table 1 (( Ahmed and Rahman, 2006 ; Bender and Hildt, 2019 ; Bottino-Rojas et al, 2018 ; Checconi et al, 2020 ; Chen et al, 2020a ; Cuadrado et al, 2020 ; Jacoby and Choi, 1994 ; Lee, 2018a ; Simenauer et al, 2019 ; Zhang et al, 2020 ).…”