Cytomegalovirus infection induces Alzheimer’s disease-associated alterations in tau
Abstract
Alzheimer's disease (AD) manifests with loss of neurons correlated with intercellular deposition of amyloid (amyloid plaques) and intracellular neurofibrillary tangles of hyperphosphorylated tau. However, targeting AD hallmarks has not as yet led to development of an effective treatment despite numerous clinical trials. A better understanding of the early stages of neurodegeneration may lead to development of more effective treatments. One underexplored area is the clinical correlation between infection with herpesviruses and increased risk of AD. We hypothesized that similar to work performed with herpes simplex virus 1 (HSV1), infection with the cytomegalovirus (CMV) herpesvirus increases levels and phosphorylation of tau, similar to AD tauopathy. We used murine CMV (MCMV) to infect mouse fibroblasts and rat neuronal cells to test our hypothesis. MCMV infection increased steady-state levels of primarily high molecular weight forms of tau and altered the patterns of tau phosphorylation. Both changes required viral late gene products. Glycogen synthase kinase 3 beta (GSK3β) was upregulated in the HSVI model, but inhibition with lithium chloride suggested that this enzyme is unlikely to be involved in MCMV infection mediated tau phosphorylation. Thus, we confirm that MCMV, a beta herpes virus, like alpha herpes viruses (e.g., HSV1), can promote tau pathology. This suggests that CMV infection can be useful as another model system to study mechanisms leading to neurodegeneration…
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Neurotropic pathogens such as human herpes virus, herpes simplex virus, hepatitis C virus, cytomegalovirus, varicella-zoster virus, and Epstein-Barr virus are associated with Alzheimer's disease neuropathology.
“For example, neurotropic pathogens, such as human herpes virus (HHV), herpes simplex virus (HSV), hepatitis C virus (HCV), cytomegalovirus, varicella-zoster virus, and Epstein–Barr virus are associated with Alzheimer’s disease (AD) neuropathology [10,11,12,13].”
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- Authors
- Mody, P. H., Marvin, K. N., Hynds, D. L., & Hanson, L. K.
- Affiliations
- Texas Woman's University (US)
- Corresponding author
- Hanson, Laura K.
- Venue
- Journal of NeuroVirology
- Published
- 2023-07-12
- Volume
- 29
- Issue
- 4
- Pages
- 400-415
- ISSN
- 1355-0284 (ISSN-L)
- 1538-2443
- OpenAlex
- W4383999230
- Cited by
- 22
- References
- 0
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 12
- FWCI
- 3.88
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Journal of NeuroVirology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Texas Woman's University (Center for Student Development)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Epidemiology › Cytomegalovirus and herpesvirus research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- cytomegalovirus, Alzheimer's disease, tau phosphorylation, tauopathy, murine cytomegalovirus, herpesvirus infection, neurodegeneration, glycogen synthase kinase-3β, lithium chloride, tau hyperphosphorylation
- MeSH terms
- Glycogen Synthase Kinase 3 beta, Alzheimer Disease, Animals, Cytomegalovirus Infections, Neurons, Phosphorylation, tau Proteins, Herpesvirus 1, Human, Mice, Rats
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