Bioenergetics of murine lungs infected with respiratory syncytial virus

Virology Journal

Abdul-Kader Souid⁶  Steven M Varga⁴  Tahir A Rizvi³  Alia Albawardi¹  Saeeda Almarzooqi¹  Stacey M Hartwig²  Farah Mustafa⁵  Jose Kochiyil⁶  Sheela Benedict⁶  Ahmed R Alsuwaidi⁶ 

[1] Departments of Pathology, College of Medicine and Health Sciences, UAE University, P.O. Box 17666, Al Ain, United Arab Emirates;Department of Microbiology, University of Iowa, Iowa City, IA, 52242, USA;Departments of Microbiology, College of Medicine and Health Sciences, UAE University, P.O. Box 17666, Al Ain, United Arab Emirates;Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA, 52242, USA;Departments of Biochemistry, College of Medicine and Health Sciences, UAE University, P.O. Box 17666, Al Ain, United Arab Emirates;Departments of Pediatrics, College of Medicine and Health Sciences, UAE University, P.O. Box 17666, Al Ain, United Arab Emirates

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

Others  :  1152293
DOI  :  10.1186/1743-422X-10-22

 received in 2012-08-25, accepted in 2013-01-11,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Alsuwaidi et al.; licensee BioMed Central Ltd.

【 图 表 】

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