Molecular consequences of peripheral Influenza A infection on cell populations in the murine hypothalamus
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Molecular consequences of peripheral Influenza A infection on cell populations in the murine hypothalamus. / Lemcke, René; Egebjerg, Christine; Berendtsen, Nicolai T; Egerod, Kristoffer L; Thomsen, Allan R; Pers, Tune H; Christensen, Jan P; Kornum, Birgitte R.
In: eLife, Vol. 12, RP87515, 2023.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Molecular consequences of peripheral Influenza A infection on cell populations in the murine hypothalamus
AU - Lemcke, René
AU - Egebjerg, Christine
AU - Berendtsen, Nicolai T
AU - Egerod, Kristoffer L
AU - Thomsen, Allan R
AU - Pers, Tune H
AU - Christensen, Jan P
AU - Kornum, Birgitte R
N1 - Publisher Copyright: © Lemcke et al.
PY - 2023
Y1 - 2023
N2 - Infection with Influenza A virus (IAV) causes the well-known symptoms of the flu, including fever, loss of appetite, and excessive sleepiness. These responses, mediated by the brain, will normally disappear once the virus is cleared from the system, but a severe respiratory virus infection may cause long-lasting neurological disturbances. These include encephalitis lethargica and narcolepsy. The mechanisms behind such long lasting changes are unknown. The hypothalamus is a central regulator of the homeostatic response during a viral challenge. To gain insight into the neuronal and non-neuronal molecular changes during an IAV infection, we intranasally infected mice with an H1N1 virus and extracted the brain at different time points. Using single-nucleus RNA sequencing (snRNA-seq) of the hypothalamus, we identify transcriptional effects in all identified cell populations. The snRNA-seq data showed the most pronounced transcriptional response at 3 days past infection, with a strong downregulation of genes across all cell types. General immune processes were mainly impacted in microglia, the brain resident immune cells, where we found increased numbers of cells expressing pro-inflammatory gene networks. In addition, we found that most neuronal cell populations downregulated genes contributing to the energy homeostasis in mitochondria and protein translation in the cytosol, indicating potential reduced cellular and neuronal activity. This might be a preventive mechanism in neuronal cells to avoid intracellular viral replication and attack by phagocytosing cells. The change of microglia gene activity suggest that this is complemented by a shift in microglia activity to provide increased surveillance of their surroundings.
AB - Infection with Influenza A virus (IAV) causes the well-known symptoms of the flu, including fever, loss of appetite, and excessive sleepiness. These responses, mediated by the brain, will normally disappear once the virus is cleared from the system, but a severe respiratory virus infection may cause long-lasting neurological disturbances. These include encephalitis lethargica and narcolepsy. The mechanisms behind such long lasting changes are unknown. The hypothalamus is a central regulator of the homeostatic response during a viral challenge. To gain insight into the neuronal and non-neuronal molecular changes during an IAV infection, we intranasally infected mice with an H1N1 virus and extracted the brain at different time points. Using single-nucleus RNA sequencing (snRNA-seq) of the hypothalamus, we identify transcriptional effects in all identified cell populations. The snRNA-seq data showed the most pronounced transcriptional response at 3 days past infection, with a strong downregulation of genes across all cell types. General immune processes were mainly impacted in microglia, the brain resident immune cells, where we found increased numbers of cells expressing pro-inflammatory gene networks. In addition, we found that most neuronal cell populations downregulated genes contributing to the energy homeostasis in mitochondria and protein translation in the cytosol, indicating potential reduced cellular and neuronal activity. This might be a preventive mechanism in neuronal cells to avoid intracellular viral replication and attack by phagocytosing cells. The change of microglia gene activity suggest that this is complemented by a shift in microglia activity to provide increased surveillance of their surroundings.
KW - Animals
KW - Mice
KW - Humans
KW - Influenza, Human
KW - Influenza A Virus, H1N1 Subtype
KW - Hypothalamus
KW - Solitary Nucleus
KW - Appetite
U2 - 10.7554/eLife.87515
DO - 10.7554/eLife.87515
M3 - Journal article
C2 - 37698546
VL - 12
JO - eLife
JF - eLife
SN - 2050-084X
M1 - RP87515
ER -
ID: 367008421