Journal
VIROLOGY
Volume 531, Issue -, Pages 183-191Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2019.03.011
Keywords
Human metapneumovirus; Metabolism; Glycolysis; TCA cycle; Virus replication
Categories
Funding
- National Institutes of Health [AI0799246, AI062885]
- [DK097153]
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Human metapneumovirus (hMPV) is an important cause of acute lower respiratory tract infections in infants, elderly and immunocompromised individuals. Ingenuity pathway analysis of microarrays data showed that 20% of genes affected by hMPV infection of airway epithelial cells (AECs) were related to metabolism. We found that levels of the glycolytic pathway enzymes hexokinase 2, pyruvate kinase M2, and lactate dehydrogenase A were significantly upregulated in normal human AECs upon hMPV infection, as well as levels of enzymes belonging to the hexosamine biosynthetic and glycosylation pathways. On the other hand, expression of the majority of the enzymes belonging to the tricarboxylic acid cycle was significantly diminished. Inhibition of hexokinase 2 and of the glycosylating enzyme O-linked N-acetylglucosamine transferase led to a significant reduction in hMPV titer, indicating that metabolic changes induced by hMPV infection play a major role during the virus life cycle, and could be explored as potential antiviral targets.
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