Herpes Simplex Virus 1 Infection of Human Brain Organoids and Pancreatic Stem Cell-Islets Drives Organoid-Specific Transcripts Associated with Alzheimer’s Disease and Autoimmune Diseases DOI Creative Commons

Jonathan Sundstrom,

Emma Vanderleeden,

Nathaniel J. Barton

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(23), P. 1978 - 1978

Published: Nov. 29, 2024

Viral infections leading to inflammation have been implicated in several common diseases, such as Alzheimer’s disease (AD) and type 1 diabetes (T1D). Of note, herpes simplex virus (HSV-1) has reported be associated with AD. We sought identify the transcriptomic changes due HSV-1 infection anti-viral drug (acyclovir, ACV) treatment of dissociated cells from human cerebral organoids (dcOrgs) versus stem cell-derived pancreatic islets (sc-islets) gain potential biological insights into relevance HSV-1-induced AD T1D. observed that differentially expressed genes (DEGs) HSV-1-infected sc-islets were enriched for autoimmune most significantly, T1D, but also rheumatoid arthritis, psoriasis, Crohn’s disease, multiple sclerosis, whereas DEGs dcOrgs exclusively The ACV was not effective rescuing transcript perturbations disease-associated genes. Finally, we identified gene ontology categories across, or unique to, viral sc-islets, involved transferase complex, mitochondrial, autophagy function. In addition, compared signatures infected coxsackie B (CVB) had T1D pathogenesis. Collectively, this study provides tissue-specific molecular effects

Language: Английский

Proteomic and transcriptomic profiling of brainstem, cerebellum and olfactory tissues in early- and late-phase COVID-19 DOI
Josefine Radke, Jenny Meinhardt, Tom Aschman

et al.

Nature Neuroscience, Journal Year: 2024, Volume and Issue: 27(3), P. 409 - 420

Published: Feb. 16, 2024

Language: Английский

Citations

34
The Promise and Potential of Brain Organoids DOI Creative Commons
Lena Smirnova, Thomas Härtung

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: 13(21)

Published: Jan. 22, 2024

Brain organoids are 3D in vitro culture systems derived from human pluripotent stem cells that self-organize to model features of the (developing) brain. This review examines techniques behind organoid generation, their current and potential applications, future directions for field. possess complex architecture containing various neural cell types, synapses, myelination. They have been utilized toxicology testing, disease modeling, infection studies, personalized medicine, gene-environment interaction studies. An emerging concept termed Organoid Intelligence (OI) combines with artificial intelligence generate learning memory, goals modeling cognition enabling biological computing applications. allow neuroscience studies not previously achievable traditional techniques, transform drug development, understanding brain development disorders. The aspirational vision OI parallels origins intelligence, efforts underway map a roadmap toward its realization. In summary, constitute disruptive technology is rapidly advancing gaining traction across multiple disciplines.

Language: Английский

Citations

22
Identification of Viral Variants from Functional Genomics Data DOI Creative Commons

Florian Röckl,

Caroline C. Friedel

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 5, 2025

The analysis of virus knockout mutants is a common approach for studying the role individual viral genes in infections and increasingly performed using functional genomics sequencing experiments, such as RNA-seq or ATAC-seq, infected cells. Identifying variants directly these experiments avoids additional genome allows confirming presence particular mutations experiment interest. Here, we present pipeline to identify from data, combining existing SNP callers with novel methods identifying deletions, insertions, corresponding inserted sequences. latter address problem that structural variant poorly on data large variations coverage. We evaluated infection wildtype Herpes simplex 1 (HSV-1) null important HSV-1 proteins. Comparison identified by our descriptions original publications showed could correctly recover introduced mutations. Thus, offers researchers fast easy way verify existence without experiments. Availability implemented workflow management system Watchdog available at https://github.com/watchdog-wms/watchdog-wms-workflows/ (VariantCallerPipeline).

Language: Английский

Citations

1
Luteolin inhibits herpes simplex virus 1 infection by activating cyclic guanosine monophosphate-adenosine monophosphate synthase-mediated antiviral innate immunity DOI
Yuan Wang, Feng Li, Zexu Wang

et al.

Phytomedicine, Journal Year: 2023, Volume and Issue: 120, P. 155020 - 155020

Published: Aug. 17, 2023

Language: Английский

Citations

18
The immunobiology of herpes simplex virus encephalitis and post-viral autoimmunity DOI Creative Commons
Jonathan Cleaver, Katie Jeffery, Paul Klenerman

et al.

Brain, Journal Year: 2023, Volume and Issue: 147(4), P. 1130 - 1148

Published: Dec. 12, 2023

Herpes simplex virus encephalitis (HSE) is the leading cause of non-epidemic in developed world and, despite antiviral therapy, mortality and morbidity high. The emergence post-HSE autoimmune reveals a new immunological paradigm autoantibody-mediated disease. A reductionist evaluation immunobiological mechanisms HSE crucial to dissect origins post-viral autoimmunity supply rational approaches selection immunotherapeutics. Herein, we review latest evidence behind phenotypic progression underlying immunobiology including cytokine/chemokine environment, role pathogen-recognition receptors, T- B-cell immunity relevant inborn errors immunity. Second, provide contemporary published patients with from combined cohort 110 patients. Third, integrate novel autoimmunization deep cervical lymph nodes explore hypotheses around challenge these against molecular mimicry others. Finally, translational concepts where neuroglial surface autoantibodies have been observed other neuroinfectious diseases those that generate brain damage traumatic injury, ischaemic stroke neurodegenerative Overall, clinical landscape an important evolving field, which precision immunotherapeutics could soon emerge.

Language: Английский

Citations

17
Effect of resveratrol on herpesvirus encephalitis: Evidences for its mechanisms of action DOI
Ziwei Huang, Shan Li,

Lishan Zhong

et al.

Phytomedicine, Journal Year: 2024, Volume and Issue: 127, P. 155476 - 155476

Published: Feb. 22, 2024

Language: Английский

Citations

6
Development of a high-throughput, quantitative platform using human cerebral organoids to study virus-induced neuroinflammation in Alzheimer’s disease DOI Creative Commons
Meagan N. Olson,

Pepper Dawes,

Liam F. Murray

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 23, 2024

ABSTRACT Neuroinflammation is a central process in the pathogenesis of several neurodegenerative diseases such as Alzheimer’s disease (AD), and there are active efforts to target pathways involved neuroinflammation for molecular biomarker discovery therapeutic development diseases. It was also proposed that may be an infectious etiology AD associated with viruses herpes simplex virus (HSV-1) influenza A (IAV), leading neuroinflammation-induced or progression. We sought develop high-throughput, quantitative assays using dissociated cells from human cerebral organoids (dcOrgs), can used screening compounds reverse AD-associated neuroinflammation. found HSV-1 infection, but not IAV dcOrgs led increased intracellular Aβ42 phosphorylated Tau-Thr212 (pTau-212) expression, lower ratios secreted Aβ42/40, well neuronal loss, proportions astrocytes microglia, which hallmarks AD. Among glia cell-type markers, Iba1 (microglia) GFAP (astrocyte) expression were most strongly correlated further supported these biomarkers perturbed by glia-mediated By performing large-scale RNA sequencing, we observed differentially expressed transcripts infected specifically enriched GWAS genes, genes other common neurodegenerative, neuropsychiatric autoimmune Immediate treatment anti-herpetic drug acyclovir (ACV) rescued cellular transcriptomic dosage-dependent manner, indicating it possible use our high-throughput platform identify

Language: Английский

Citations

4
Exposure to PFOA, PFOS, and PFHxS induces Alzheimer's disease-like neuropathology in cerebral organoids DOI

Shiya Lu,

Xizhi Zhu,

Pinli Zeng

et al.

Environmental Pollution, Journal Year: 2024, Volume and Issue: 363, P. 125098 - 125098

Published: Oct. 9, 2024

Language: Английский

Citations

4
Structural variation, selection, and diversification of theNPIPgene family from the human pangenome DOI Creative Commons
Philip C. Dishuck, Katherine M. Munson, Alexandra P. Lewis

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 5, 2025

ABSTRACT The NPIP (nuclear pore interacting protein) gene family has expanded to high copy number in humans and African apes where it been subject an excess of amino acid replacement consistent with positive selection (1). Due the limitations short-read sequencing, human genetic diversity poorly understood. Using highly accurate assemblies generated from long-read sequencing as part pangenome, we completely characterize 169 haplotypes (4,665 paralogs alleles). Of 28 paralogs, just three ( NPIPB2 , B11 B14 ) are fixed at a single copy, only locus, B2 shows no structural variation. Four map large segmental duplication blocks that mediate polymorphic inversions (355 kbp–1.6 Mbp) corresponding microdeletions associated developmental delay autism. Haplotype-based tests selective sweeps identify two B9 B15 within top percentile for both tests. full-length cDNA data 101 tissue/cell types, construct paralog-specific models show 56% (31/55 most abundant isoforms) have not previously described RefSeq. We define six distinct translation start sites other protein features distinguish including variable tandem repeat encodes beta helix size emerged ∼3.1 million years ago evolution. Among tissue patterns expression few maintaining ancestral testis-enriched expression. A subset NPIPA1 A5 A6-9 B3-5 B12/B13 increased brain Our results suggest ongoing population rapid diversification models.

Language: Английский

Citations

0
Organoid Models to Study Human Infectious Diseases DOI Creative Commons

Sijing Zhu,

Dan Chen,

Xinzhi Yang

et al.

Cell Proliferation, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 20, 2025

ABSTRACT Infectious diseases have become significant events that threaten global public health and economic development. Since the 20th century, multiple outbreaks of infectious gradually deepened humanity's understanding viral infections, prevention treatment. Organoids possess a high degree similarity to human physiological states strong self‐organising capabilities. Research on based organoids offers advantages in terms availability, editability diversity. In this perspective, we briefly introduce development organoids, focusing historically caused fatal harm health, such as HIV, ZIKV, SARS‐CoV‐2 MPXV. We further summarise relevant research pathogenic mechanisms these viruses organoid models, host reactivity, therapeutic strategies. Finally, list latest techniques combined with discuss challenges faced look forward future prospects vaccine drug

Language: Английский

Citations

0