Bioenergetics of murine lungs infected with respiratory syncytial virus

Abstract

Doc number: 22

Abstract

Background: Cellular bioenergetics (cellular respiration and accompanying ATP synthesis) is a highly sensitive biomarker of tissue injury and may be altered following infection. The status of cellular mitochondrial O₂ consumption of the lung in pulmonary RSV infection is unknown.

Methods: In this study, lung fragments from RSV-infected BALB/c mice were evaluated for cellular O₂ consumption, ATP content and caspase activity. The disease was induced by intranasal inoculation with the RSV strain A2 and lung specimens were analyzed on days 2-15 after inoculation. A phosphorescence O₂ analyzer that measured dissolved O₂ concentration as a function of time was used to monitor respiration. The caspase-3 substrate analogue N -acetyl-asp-glu-val-asp-7-amino-4-methylcoumarin (Ac-DEVD-AMC) was used to monitor intracellular caspases.

Results: O₂ concentration declined linearly with time when measured in a sealed vial containing lung fragment and glucose as a respiratory substrate, revealing its zero-order kinetics. O₂ consumption was inhibited by cyanide, confirming the oxidation occurred in the respiratory chain. Cellular respiration increased by 1.6-fold (p <0.010) and ATP content increased by 3-fold in the first week of RSV infection. Both parameters returned to levels found in uninfected lungs in the second week of RSV infection. Intracellular caspase activity in infected lungs was similar to uninfected lungs throughout the course of disease.

Conclusions: Lung tissue bioenergetics is transiently enhanced in RSV infection. This energy burst, triggered by the virus or virus-induced inflammation, is an early biomarker of the disease and may be targeted for therapy.