Recurrent herpes simplex virus-1 infection induces hallmarks of neurodegeneration and cognitive deficits in mice
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Herpes simplex virus type 1 (HSV-1) is a DNA neurotropic virus, usually establishing latent infections in the trigeminal ganglia followed by periodic reactivations. Although numerous findings suggested potential links between HSV-1 and Alzheimer's disease (AD), a causal relation has not been demonstrated yet. Hence, we set up a model of recurrent HSV-1 infection in mice undergoing repeated cycles of viral reactivation. By virological and molecular analyses we found: i) HSV-1 spreading and replication in different brain regions after thermal stress-induced virus reactivations; ii) accumulation of AD hallmarks including amyloid-β protein, tau hyperphosphorylation, and neuroinflammation markers (astrogliosis, IL-1β and IL-6). Remarkably, the progressive accumulation of AD molecular biomarkers in neocortex and hippocampus of HSV-1 infected mice, triggered by repeated virus reactivations, correlated with increasing cognitive deficits becoming irreversible after seven cycles of reactivation. Collectively, our findings provide evidence that mild and recurrent HSV-1 infections in the central nervous system produce an AD-like phenotype and suggest that they are a risk factor for AD.
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In mice with recurrent HSV-1 infection, HSV-1 spreads and proliferates in different brain regions following reactivation by thermal stress, accompanied by Aβ deposition, tau hyperphosphorylation and neuroinflammation.
“In mice with recurrent HSV-1 infection, HSV-1 was shown to spread and proliferate in different brain regions following reactivation by thermal stress. This was accompanied by the occurrence of pathological events associated with AD including Aβ deposition, tau hyperphosphorylation and neuroinflammation [534].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [534]
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- Authors
- De Chiara, G., Piacentini, R., Fabiani, M., Mastrodonato, A., Marcocci, M. E., Limongi, D., Napoletani, G., Protto, V., Coluccio, P., Celestino, I., Li Puma, D. D., Grassi, C., & Palamara, A. T.
- Affiliations
- Università Cattolica del Sacro Cuore (IT)
- Istituto Pasteur (IT)
- IRCCS San Raffaele Roma (IT)
- Istituto di Farmacologia Traslazionale (IT)
- ORCID
- Venue
- PLOS Pathogens
- Publisher
- Public Library of Science (PLoS)
- Published
- 2019-03-14
- Volume
- 15
- Issue
- 3
- Pages
- e1007617
- ISSN
- 1553-7366 (ISSN-L)
- 1553-7374
- PMC
- PMC6417650
- OpenAlex
- W2921910376
- Cited by
- 266
- References
- 70
- Citations by year
- 2026: 33 · 2025: 34 · 2024: 38 · 2023: 26 · 2022: 44 · 2021: 42 · 2020: 36 · 2019: 12 · 2018: 1
- FWCI
- 22.90
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS Pathogens (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Florence Research (University of Florence) (submittedVersion)
- PubliCatt (Università Cattolica del Sacro Cuore) (submittedVersion, cc-by)
- Funders
- Ministero dell’Istruzione, dell’Università e della Ricerca (PRIN2015W729WH_001, PRIN2015W729WH_005)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Epidemiology › Herpesvirus Infections and Treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- herpes simplex virus type 1, Alzheimer's disease, neurodegeneration, cognitive impairment, amyloid-beta, tau hyperphosphorylation, neuroinflammation, astrocyte activation, IL-1β, interleukin-6, hippocampus, neocortex, thermal stress (biology)
- MeSH terms
- Alzheimer Disease, Animals, Brain, Cognition, Cognition Disorders, Disease Models, Animal, Female, Mice, Inbred BALB C, Trigeminal Ganglion, Virus Activation, Virus Replication, Amyloid beta-Peptides, Herpesvirus 1, Human, Neurodegenerative Diseases, Mice, Cognitive Dysfunction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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