Respiratory infection with influenza A virus delays remyelination and alters oligodendrocyte metabolism
Allison Y. Louie,
Jenny Drnevich,
Jennifer L. Johnson,
Meagan Woodard,
Anna V. Kukekova,
Rodney W. Johnson,
Andrew J. Steelman
Affiliations
Allison Y. Louie
Neuroscience Program, University of Illinois at Urbana-Champaign, Urbana, IL, USA
Jenny Drnevich
Roy J. Carver Biotechnology Center, University of Illinois at Urbana-Champaign, Urbana, IL, USA
Jennifer L. Johnson
Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA
Meagan Woodard
Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA
Anna V. Kukekova
Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA
Rodney W. Johnson
Neuroscience Program, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA
Andrew J. Steelman
Neuroscience Program, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Corresponding author
Summary: Peripheral viral infection disrupts oligodendrocyte (OL) homeostasis such that endogenous remyelination may be affected. Here, we demonstrate that influenza A virus infection perpetuated a demyelination- and disease-associated OL phenotype following cuprizone-induced demyelination that resulted in delayed OL maturation and remyelination in the prefrontal cortex. Furthermore, we assessed cellular metabolism ex vivo, and found that infection altered brain OL and microglia metabolism in a manner that opposed the metabolic profile induced by remyelination. Specifically, infection increased glycolytic capacity of OLs and microglia, an effect that was recapitulated by lipopolysaccharide (LPS) stimulation of mixed glia cultures. In contrast, mitochondrial dependence was increased in OLs during remyelination, which was similarly observed in OLs of myelinating P14 mice compared to adult and aged mice. Collectively, our data indicate that respiratory viral infection is capable of suppressing remyelination, and suggest that metabolic dysfunction of OLs is implicated in remyelination impairment.
