Oxidative stress in Nipah virus-infected human small airway epithelial cells

Abstract

Nipah virus (NiV) is a zoonotic emerging pathogen that can cause severe and often fatal respiratory disease in humans. The pathogenesis of NiV infection of the human respiratory tract remains unknown. Reactive oxygen species (ROS) produced by airway epithelial cells in response to viral infections contribute to lung injury by inducing inflammation and oxidative stress; however, the role of ROS in NiV-induced respiratory disease is unknown. To investigate whether NiV induces oxidative stress in human respiratory epithelial cells, we used oxidative stress markers and monitored antioxidant gene expression. We also used ROS scavengers to assess their role in immune response modulation. Oxidative stress was confirmed in infected cells and correlated with the reduction in antioxidant enzyme gene expression. Infected cells treated by ROS scavengers resulted in a significant decrease of the (F 2 )-8-isoprostane marker, inflammatory responses and virus replication. In conclusion, ROS are induced during NiV infection in human respiratory epithelium and contribute to the inflammatory response. Understanding how oxidative stress contributes to NiV pathogenesis is crucial for therapeutic development.

Contribution of Human Lung Parenchyma and Leukocyte Influx to Oxidative Stress and Immune System-Mediated Pathology following Nipah Virus Infection

“…Interestingly, the total activity of SOD, as measured for three subtypes (SOD1, -2, and -3) involved in cellular defenses that control oxidative stress, was decreased late during infection. This is consistent with our previous findings showing gene downregulation of SOD2 and SOD3 in respiratory epithelial cells (19), suggesting that reduced SOD activity contributes to an increased level of reactive oxygen species (ROS), the actors of oxidative stress that cause cellular oxidative damage across the lung at a late stage of infection. However, the earlier induction of oxidative stress in NiV-B-infected lung grafts from reconstituted mice suggests that human leukocytes also contribute to oxidative stress when recruited to the site of infection.…”

“…Based on all these observations, NiV infection of human lung grafts results in an outcome reminiscent of ALI, suggesting that human lung grafts in the reconstituted mouse model constitute a robust model that recapitulates typical pulmonary histopathological lesions observed in NiV-infected patients. We previously reported that NiV-B induces oxidative stress in epithelial cells from human small airways (19). Here, we demonstrated that oxidative stress also occurs in NiV-B-infected human lung grafts by quantifying MDA-protein adducts, a well-accepted oxidative stress marker (47)(48)(49).…”

“…NiV-B-induced oxidative stress was previously shown to play a role in inflammation in infected human respiratory epithelium (19), suggesting that oxidative stress contributes to NiV-induced ALI. Here, the formation of malondialdehyde (MDA)-protein adducts was quantified in lung grafts and used as a marker of oxidative stress.…”

“…These features were also found in NiV-Minfected human lung xenografts (15) and in lungs of several animal models, such as Syrian hamsters, ferrets, and African Green monkeys (10,13,(16)(17)(18), demonstrating the suitability of these models for the study of NiV pathogenesis. Previously, we demonstrated in vitro that NiV-B infection of primary human small airway epithelial cells caused a strong inflammatory response, in part induced by oxidative stress (19), that was accompanied by cell damage and chemotaxis of mononuclear cells (12,20). We also showed that the tracheal bronchial epithelium could contribute to virus spread (12).…”

A disrupted transsulphuration pathway results in accumulation of redox metabolites and induction of gametocytogenesis in malaria

“…The ability to shift the redox homeostasis of the host is shared by many other viruses, bacteria and protozoa. As shown in Table 1, many infections caused by intracellular pathogens result in a 2-4-fold decrease in the GSH: GSSG ratio of the host cell221222324252627282930313233. Importantly, this altered redox state is often utilized by the pathogen to facilitate its pathogenesis and/or transmission.…”