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Open Access Research

Bioenergetics of murine lungs infected with respiratory syncytial virus

Ahmed R Alsuwaidi1, Sheela Benedict1, Jose Kochiyil1, Farah Mustafa2, Stacey M Hartwig5, Saeeda Almarzooqi3, Alia Albawardi3, Tahir A Rizvi4, Steven M Varga567* and Abdul-Kader Souid1*

Author Affiliations

1 Departments of Pediatrics, College of Medicine and Health Sciences, UAE University, P.O. Box 17666, Al Ain, United Arab Emirates

2 Departments of Biochemistry, College of Medicine and Health Sciences, UAE University, P.O. Box 17666, Al Ain, United Arab Emirates

3 Departments of Pathology, College of Medicine and Health Sciences, UAE University, P.O. Box 17666, Al Ain, United Arab Emirates

4 Departments of Microbiology, College of Medicine and Health Sciences, UAE University, P.O. Box 17666, Al Ain, United Arab Emirates

5 Department of Microbiology, University of Iowa, Iowa City, IA, 52242, USA

6 Department of Pathology, University of Iowa, Iowa City, IA, 52242, USA

7 Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA, 52242, USA

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Virology Journal 2013, 10:22  doi:10.1186/1743-422X-10-22

Published: 15 January 2013

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.

Keywords:
Respiratory syncytial virus (RSV); Cellular respiration; Oxygen consumption; Cellular ATP; Mitochondria; Caspases