Oxidative Stress in Poultry: Lessons from the Viral Infections

Abstract

Reactive species (RS), generally known as reactive oxygen species (ROS) and reactive nitrogen species (RNS), are produced during regular metabolism in the host and are required for many cellular processes such as cytokine transcription, immunomodulation, ion transport, and apoptosis. Intriguingly, both RNS and ROS are commonly triggered by the pathogenic viruses and are famous for their dual roles in the clearance of viruses and pathological implications. Uncontrolled production of reactive species results in oxidative stress and causes damage in proteins, lipids, DNA, and cellular structures. In this review, we describe the production of RS, their detoxification by a cellular antioxidant system, and how these RS damage the proteins, lipids, and DNA. Given the widespread importance of RS in avian viral diseases, oxidative stress pathways are of utmost importance for targeted therapeutics. Therefore, a special focus is provided on avian virus-mediated oxidative stresses. Finally, future research perspectives are discussed on the exploitation of these pathways to treat viral diseases of poultry.

Figure 1

Basic mechanisms of viral cross-talk with the cellular pathways to cause oxidative damage to cellular components. After entry into the cells, viral particles like proteins or nucleic acids are recognised by the pattern recognition receptors. Viral recognition as well as replication initiates the stress signalling and sends signal to the mitochondria and NOX2 and activates the NF-κB. After receiving the stress signals, NOX2 initiates the production of superoxides (O₂⁻), and dysfunctioning in the mitochondrial proteins function occurs. These defective mitochondrial proteins result in the leakage of electrons and superoxides from the mitochondria, as well as initiating the cell death pathways by cytochrome c (cyt c) or permeability transition pore (PTP). The NF-κB-induced transcription is initiated by the NF-κB resulting in the production of many cytokines as well as inducible NO synthase (iNOS). This iNOS produces large amounts of nitric oxide (NO). The NO and O₂⁻ react together to produce peroxynitrite (ONOO) which is a highly reactive compound and can cause the protein nitration, lipid peroxidation, DNA damage, and viral mutations. Similarly, higher production of O₂⁻ results in the production of H₂O₂ by the catalytic activity of superoxide dismutase (SOD). Uncontrolled production of H₂O₂ produces hydroxyl radicals (OH-) via reaction with metal cations, and these H₂O₂ and OH- cause irreversible damage to cellular macromolecules: proteins, lipids, nucleic acids, etc.

Scheme 1

Production of ROS and Fenton reaction.

Scheme 2

Lipid peroxidation mechanism.

Figure 2

The scheme summarizes the effect of common avian viruses on the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS). After viral insult, cells recognise them by different pattern recognition receptors and enhance the production of ROS/RNS species, which are involved in the cell migration, cell signalling, macrophage polarization, requirement of immune cells, and importantly clearance to host from invading pathogens. But in chronic or overproduction of viruses, hijack the production of ROS/RNS by disturbing different cellular pathways/organelles like mitochondrial metabolism, leading to a decrease the activity/level of cellular enzymatic and nonenzymatic antioxidants. It leads to increased pathological damage in poultry. It leads to increased pathological damage in poultry.