Increased mortality from influenza infection in long-chain acyl-CoA dehydrogenase knockout mice.
Biochem Biophys Res Commun
; 497(2): 700-704, 2018 03 04.
Article
em En
| MEDLINE
| ID: mdl-29458021
ABSTRACT
We previously showed that the mitochondrial fatty acid oxidation enzyme long-chain acyl-CoA dehydrogenase (LCAD) is expressed in alveolar type II pneumocytes and that LCAD-/- mice have altered breathing mechanics and surfactant defects. Here, we hypothesized that LCAD-/- mice would be susceptible to influenza infection. Indeed, LCAD-/- mice demonstrated increased mortality following infection with 2009 pandemic influenza (A/CA/07/09). However, the mortality was not due to increased lung injury, as inflammatory cell counts, viral titers, and histology scores all showed non-significant trends toward milder injury in LCAD-/- mice. To confirm this, LCAD-/- were infected with a second, mouse-adapted H1N1 virus (A/PR/8/34), to which they responded with significantly less lung injury. While both strains become increasingly hypoglycemic over the first week post-infection, LCAD-/- mice lose body weight more rapidly than wild-type mice. Surprisingly, while acutely fasted LCAD-/- mice develop hepatic steatosis, influenza-infected LCAD-/- mice do not. They do, however, become more hypothermic than wild-type mice and demonstrate increased blood lactate values. We conclude that LCAD-/- mice succumb to influenza from bioenergetic starvation, likely due to increased reliance upon glucose for energy.
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Base de dados:
MEDLINE
Assunto principal:
Infecções por Orthomyxoviridae
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Acil-CoA Desidrogenase de Cadeia Longa
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Vírus da Influenza A Subtipo H1N1
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Técnicas de Silenciamento de Genes
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Pulmão
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article