Redox Biology of Respiratory Viral Infections

Olga A Khomich, Sergey N Kochetkov, Birke Bartosch, Alexander V Ivanov, Olga A Khomich, Sergey N Kochetkov, Birke Bartosch, Alexander V Ivanov

Abstract

Respiratory viruses cause infections of the upper or lower respiratory tract and they are responsible for the common cold-the most prevalent disease in the world. In many cases the common cold results in severe illness due to complications, such as fever or pneumonia. Children, old people, and immunosuppressed patients are at the highest risk and require fast diagnosis and therapeutic intervention. However, the availability and efficiencies of existing therapeutic approaches vary depending on the virus. Investigation of the pathologies that are associated with infection by respiratory viruses will be paramount for diagnosis, treatment modalities, and the development of new therapies. Changes in redox homeostasis in infected cells are one of the key events that is linked to infection with respiratory viruses and linked to inflammation and subsequent tissue damage. Our review summarizes current knowledge on changes to redox homeostasis, as induced by the different respiratory viruses.

Keywords: Nrf2; inflammation; influenza virus; oxidative stress; reactive oxygen species; respiratory syncytial virus; rhinovirus.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Sources of reactive oxygen species (ROS) in airway epithelial cells infected with influenza virus (IV, the left cell) or human respiratory syncytial virus (HRSV) and rhinovirus (HRV, the right cell). Cellular events, triggered by ROS production, are detailed in the text. The sources are mainly represented by nicotinamide adenine dinucleotide phosphate oxidases (NADPH oxidases, Nox), Dual oxidase (Duox) and xanthine oxidase (XO). Respiratory viruses also contribute to the production of superoxide anion by Nox2, an enzyme expressed in macrophages and, to a lesser extent, in epithelial cells.
Figure 2
Figure 2
Mechanisms of cytokine production (cytokine storm) and epithelial barrier disruption by respiratory viruses. Infection leads to the enhanced ROS production that may trigger cell death and subsequent macrophage activation. This activation is accompanied by cytokine production leading to the inflammation and destruction of epithelial cell contacts. Proinflammatory cytokines could also be produced by infected cells via activation of redox-sensitive nuclear factor kappa B (NFκB) pathway that drives transcription of their genes and via activation of NLRP3 inflammasome in ROS-dependent manner that mediates maturation and secretion of cytokines. Disruption of epithelial barrier results in the increased susceptibility to bacterial infection.

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