Long-Term Neuroinflammation Induced by Influenza A Virus Infection and the Impact on Hippocampal Neuron Morphology and Function.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
MetadataShow full item record
AbstractAcute influenza infection has been reported to be associated with neurological symptoms. However, the long-term consequences of an infection with neurotropic and non-neurotropic influenza A virus (IAV) variants for the CNS remain elusive. We can show that spine loss in the hippocampus after infection with neurotropic H7N7 (rSC35M) and non-neurotropic H3N2 (maHK68) in female C57BL/6 mice persists well beyond the acute phase of the disease. Although spine number was significantly reduced at 30 d postinfection (dpi) with H7N7 or H3N2, full recovery could only be observed much later at 120 dpi. Infection with H1N1 virus, which was shown previously to affect spine number and hippocampus-dependent learning acutely, had no significant long-term effects. Spine loss was associated with an increase in the number of activated microglia, reduced long-term potentiation in the hippocampus, and impairment in spatial memory formation, indicating that IAV-associated inflammation induced functional and structural alterations in hippocampal networks. Transcriptome analyses revealed regulation of many inflammatory and neuron- and glia-specific genes in H3N2- and H7N7-infected mice at day 18 and in H7N7-infected mice at day 30 pi that related to the structural and functional alterations. Our data provide evidence that neuroinflammation induced by neurotropic H7N7 and infection of the lung with a non-neurotropic H3N2 IAV result in long-term impairments in the CNS. IAV infection in humans may therefore not only lead to short-term responses in infected organs, but may also trigger neuroinflammation and associated chronic alterations in the CNS.SIGNIFICANCE STATEMENT In the acute phase of influenza infection, neuroinflammation can lead to alterations in hippocampal neuronal morphology and cognitive deficits. The results of this study now also provide evidence that neuroinflammation induced by influenza A virus (IAV) infection can induce longer-lasting, virus-specific alterations in neuronal connectivity that are still detectable 1 month after infection and are associated with impairments in spatial memory formation. IAV infection in humans may therefore not only lead to short-term responses in infected organs, but may also trigger neuroinflammation and associated chronic alterations in the CNS.
Citation. J Neurosci. 2018;38(12):3060-3080. doi:10.1523/JNEUROSCI.1740-17.2018.
AffiliationHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
PublisherSociety for Neuroscience
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-ShareAlike 4.0 International
- Long-Term Consequence of Non-neurotropic H3N2 Influenza A Virus Infection for the Progression of Alzheimer's Disease Symptoms.
- Authors: Hosseini S, Michaelsen-Preusse K, Schughart K, Korte M
- Issue date: 2021
- Influenza infection induces neuroinflammation, alters hippocampal neuron morphology, and impairs cognition in adult mice.
- Authors: Jurgens HA, Amancherla K, Johnson RW
- Issue date: 2012 Mar 21
- Induction of microglia activation after infection with the non-neurotropic A/CA/04/2009 H1N1 influenza virus.
- Authors: Sadasivan S, Zanin M, O'Brien K, Schultz-Cherry S, Smeyne RJ
- Issue date: 2015
- Inflammatory response of mast cells during influenza A virus infection is mediated by active infection and RIG-I signaling.
- Authors: Graham AC, Hilmer KM, Zickovich JM, Obar JJ
- Issue date: 2013 May 1
- Inhibition of lung serine proteases in mice: a potentially new approach to control influenza infection.
- Authors: Bahgat MM, Błazejewska P, Schughart K
- Issue date: 2011 Jan 20