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Type I interferons mediate pathogenic reactive oxygen species during neonatal influenza virus infection
Journal article   Peer reviewed

Type I interferons mediate pathogenic reactive oxygen species during neonatal influenza virus infection

Ogan K Kumova and Alison J Carey
The Journal of immunology (1950), v 204(1_Supplement), pp 171-171.4
01 May 2020
DOI: https://doi.org/10.4049/jimmunol.204.Supp.171.4

Abstract

Abstract Infants less than six months of age are particularly susceptible to respiratory viral infection-associated morbidity and mortality. Type I Interferons, IFN I, a potent anti-viral cytokine which controls viral replication, can also result in the production of pathogenic reactive oxygen species, ROS. Infants are particularly susceptible to ROS because of immature antioxidant production, such as superoxide dismutase 3, and demonstrate increased pathology under oxidative stress conditions. Using our previously established neonatal mouse influenza virus model, we sought to determine if IFN I was protective or deleterious in neonatal influenza virus infection. Three-day old neonatal IFN I receptor, IFNAR-deficient and C57Bl/6 mice were infected with PR8, H1N1 influenza virus and tracked for survival. IFNAR deficient neonatal mice had improved survival, 80% survival versus 20% survival in C57Bl/6 pups. To determine the mechanism of IFN I toxicity, pulmonary type II epithelial cells were isolated 48 hours post-infection and IFNb was applied to the epithelial cells ex vivo. A flow cytometric CellROX assay was performed to determine production of ROS. When exposed to IFNb, neonatal lung epithelial cells produce more ROS than adult lung cells. To determine if an antioxidant could mitigate oxidative stress during in vivo neonatal influenza virus infection, 3 day old murine neonates were treated with an antioxidant, N-acetyl cysteine, NAC, after influenza virus infection. Survival improved from 10% in sham-treated pups to 60% in NAC-treated pups. We speculate that IFN I-induced ROS, coupled with the neonatal inability to neutralize ROS, increases mortality in this vulnerable population.

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