Herpes simplex virus‐1 infection alters microtubule‐associated protein Tau splicing and promotes Tau pathology in neural models of Alzheimer's disease DOI Creative Commons
Emmanuel C. Ijezie, Michael J. Miller, Céline Hardy

et al.

Brain Pathology, Journal Year: 2025, Volume and Issue: unknown

Published: March 26, 2025

Herpes simplex virus 1 (HSV-1) infection alters critical markers of Alzheimer's disease (AD) in neurons. One key marker AD is the hyperphosphorylation Tau, accompanied by altered levels Tau isoforms. However, an imbalance these splice variants, specifically resulting from 3R to 4R MAPT splicing exon 10, has yet be directly associated with HSV-1 infection. To this end, we infected 2D and 3D human neural models monitored phosphorylation. Further, transduced SH-SY5Y neurons ICP27, which RNA splicing, analyze if ICP27 alone sufficient induce 10 splicing. We show that induces increasing 4R-Tau protein levels, hyperphosphorylation, oligomerization. Our experiments reveal a novel link between development cytopathic phenotypes linked progression.

Language: Английский

A natural experiment on the effect of herpes zoster vaccination on dementia DOI Creative Commons
Markus Eyting, Min Xie, Felix Michalik

et al.

Nature, Journal Year: 2025, Volume and Issue: unknown

Published: April 2, 2025

Neurotropic herpesviruses may be implicated in the development of dementia1-5. Moreover, vaccines have important off-target immunological effects6-9. Here we aim to determine effect live-attenuated herpes zoster vaccination on occurrence dementia diagnoses. To provide causal as opposed correlational evidence, take advantage fact that, Wales, eligibility for vaccine was determined basis an individual's exact date birth. Those born before 2 September 1933 were ineligible and remained life, whereas those or after eligible at least 1 year receive vaccine. Using large-scale electronic health record data, first show that percentage adults who received increased from 0.01% among patients merely week too old eligible, 47.2% just younger. Apart this large difference probability ever receiving vaccine, individuals are unlikely differ systematically later. these comparison groups a regression discontinuity design, reduced new diagnosis over follow-up period 7 years by 3.5 points (95% confidence interval (CI) = 0.6-7.1, P 0.019), corresponding 20.0% CI 6.5-33.4) relative reduction. This protective stronger women than men. We successfully confirm our findings different population (England Wales's combined population), with type data (death certificates) using outcome (deaths primary cause) is closely related dementia, but less reliant timely healthcare system10. Through use unique natural experiment, study provides evidence dementia-preventing dementia-delaying vulnerable confounding bias existing associational evidence.

Language: Английский

Citations

2
Phosphorylated-tau associates with HSV-1 chromatin and correlates with nuclear speckles decondensation in low-density host chromatin regions DOI Creative Commons
Leonardo D’Aiuto,

Jill K. Caldwell,

Terri G. Edwards

et al.

Neurobiology of Disease, Journal Year: 2025, Volume and Issue: unknown, P. 106804 - 106804

Published: Jan. 1, 2025

Abnormal tau phosphorylation is a key mechanism in neurodegenerative diseases. Evidence implicates infectious agents, such as Herpes Simplex Virus 1 (HSV-1), co-factors the onset or progression of diseases, including Alzheimer's disease. This has led to divergence field regarding contribution viruses etiology Research indicates that may function risk factors driving disease rather than playing causative role. Investigating HSV-1 abnormal important for understanding role agents neurodegeneration. We generated cellular models acute, latent infection, and viral reactivation from latency cortical brain organoids investigated interplay between infection by employing human induced pluripotent stem cell (iPSC)-derived monolayer neuronal cultures organoids. Acute with strains 17syn+ KOS caused nuclear accumulation phosphorylated (p-tau) neurons neural precursor cells. Antivirals prevented p-tau. Viral was accompanied translocation Chromatin immunoprecipitation analysis indicated an interaction p-tau chromatin. A reduction abundance component speckles their loss organized morphology low host chromatin density regions observed, strain-specific differences. followed increase BRSKs TAOKs, kinases known phosphorylate tau. These findings show demonstrate ability activate mechanisms are observed

Language: Английский

Citations

1
HSV and a tale of two taus DOI

Leslie K. Ferrarelli

Science Signaling, Journal Year: 2025, Volume and Issue: 18(869)

Published: Jan. 14, 2025

Tau aggregates around HSV-1 in the brain, but is this pathological, part of an immune response, or both?

Language: Английский

Citations

0
Infections, Genetics, and Alzheimer's Disease: Exploring the Pathogenic Factors for Innovative Therapies DOI

Ramesh Kordi,

T. John Andrews,

Mark D. Hicar

et al.

Virology, Journal Year: 2025, Volume and Issue: unknown, P. 110523 - 110523

Published: March 1, 2025

Language: Английский

Citations

0
Neurotropic Viruses as Acute and Insidious Drivers of Aging DOI Creative Commons
Angela Rocchi, Hassen S. Wollebo, Kamel Khalili

et al.

Biomolecules, Journal Year: 2025, Volume and Issue: 15(4), P. 514 - 514

Published: April 1, 2025

Aging is the result of various compounding stresses that gradually overcome homeostatic regulation cell, resulting in irreversible damage. This manifests as many acute and chronic conditions, most common which are neurodegeneration dementia. Epidemiological studies have shown significant, strong correlations between viral infection neurodegenerative diseases. review overlays characteristics pathogenesis with hallmarks aging to discuss how active latent viruses contribute aging. Through our contextualization myriad basic science papers, we offer explanations for premature via induction stress response pathways. Viruses induce stresses: dysregulated homeostasis by exogenous proteins overwhelmed protein quality control mechanisms, DNA damage through direct integration epigenetic manipulation, immune-mediated oxidative immune exhaustion, general energy theft amplified an system. Overall, this highlights long-term importance vaccines antivirals addition their benefits.

Language: Английский

Citations

0
L’herpès en cause dans Alzheimer ? DOI

Bénédicte Salthun-Lassalle

Cerveau & Psycho, Journal Year: 2025, Volume and Issue: Nº 175(4), P. 12 - 12

Published: March 11, 2025

Citations

0
Herpes simplex virus‐1 infection alters microtubule‐associated protein Tau splicing and promotes Tau pathology in neural models of Alzheimer's disease DOI Creative Commons
Emmanuel C. Ijezie, Michael J. Miller, Céline Hardy

et al.

Brain Pathology, Journal Year: 2025, Volume and Issue: unknown

Published: March 26, 2025

Herpes simplex virus 1 (HSV-1) infection alters critical markers of Alzheimer's disease (AD) in neurons. One key marker AD is the hyperphosphorylation Tau, accompanied by altered levels Tau isoforms. However, an imbalance these splice variants, specifically resulting from 3R to 4R MAPT splicing exon 10, has yet be directly associated with HSV-1 infection. To this end, we infected 2D and 3D human neural models monitored phosphorylation. Further, transduced SH-SY5Y neurons ICP27, which RNA splicing, analyze if ICP27 alone sufficient induce 10 splicing. We show that induces increasing 4R-Tau protein levels, hyperphosphorylation, oligomerization. Our experiments reveal a novel link between development cytopathic phenotypes linked progression.

Language: Английский

Citations

0