Influenza infection disrupts oligodendrocyte homeostasis and alters the myelin lipidome in the adult mouse central nervous system.

The notion that myelin remains static during adulthood has been challenged in recent years, and it is increasingly recognized that myelin may be altered by physiological events occurring outside of the central nervous system resulting in changes to cognition and behavior. The consequences of influenza A virus infection on oligodendrocytes in the adult mouse were investigated. Transcriptomic analysis revealed global downregulation and subsequent recovery of oligodendrocyte-specific transcripts in response to peripheral viral infection. Infection neither affected myelin thickness nor oligodendrocyte survival in the mPFC but altered the oligodendrocyte proteome and increased a disease-specific marker associated with oligodendrocyte stress. Furthermore, shot-gun lipidomic analysis revealed that infection altered the lipid profile in the prefrontal cortex as well as in purified brain myelin. Finally, treatment with the CSF1R antagonist GW2580 suppressed glial activation and partially restored oligodendrocyte-specific transcripts to baseline levels during infection. Together, these findings show that peripheral immunological challenge altered oligodendrocyte physiology. Female C57BL/6J mice were inoculated with PBS (n=1) or influenza A virus (n=1; A/PR8/34; 1.0 HAU). At day 8 post-infection, mice were euthanized by CO2 asphyxiation, intracardially perfused with 20 ml of ice cold artificial cerebrospinal fluid, and then the brain was extracted. The whole brain was dissociated and viable single cell suspensions prepared with debris/myelin removed. Cells were analyzed using scRNA-seq.