Evidence map›Paper›PMID 40770351›Full record

ArticleStem cell research & therapy2025

Zika virus impairs non-homologous end joining and exacerbates DNA damage in neural progenitors derived from Huntington's disease iPSCs via mutant huntingtin-elicited Ku70/Ku80 complex disruption.

Feng-Lan Chiu, Jian-Jong Liang, Yi-Ling Lin, Hung-Chih Kuo

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Article in Stem cell research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

4 authors.

Feng-Lan ChiuInstitute of Cellular and Organismic Biology, Academia Sinica, Taipei, 11529, Taiwan.
Jian-Jong LiangInstitute of Biomedical Sciences, Academia Sinica, Taipei, 11529, Taiwan.
Yi-Ling LinInstitute of Biomedical Sciences, Academia Sinica, Taipei, 11529, Taiwan.
Hung-Chih KuoInstitute of Cellular and Organismic Biology, Academia Sinica, Taipei, 11529, Taiwan. kuohuch@gate.sinica.edu.tw.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundZika virus (ZIKV) preferentially infects neural progenitor cells (NPCs) and is associated with NPC depletion in neonates. However, the impacts of ZIKV infection on NPCs in the context of neurodegenerative disease such as Huntington's disease (HD) remains poorly understood.

methodsTo investigate the effects of ZIKV on NPCs from individuals with HD, induced pluripotent stem cells (iPSCs) derived from HD patients were differentiated into NPCs (HD-iPSC-NPCs) in vitro. The phenotypic characterization of HD-iPSC-NPCs was performed using reverse transcription polymerase chain reaction (RT-PCR), Western blotting, and immunocytochemistry. Additionally, potential interactions between Ku70 and huntingtin were assessed using proximity ligation assay (PLA) and co-immunoprecipitation (co-IP).

resultsWe demonstrated that ZIKV infection increased mutant huntingtin (mHTT) expression through upregulation of SP1 expression. Furthermore, HD-iPSC-NPCs were susceptible to ZIKV-induced DNA double-strand breaks and cell apoptosis due to an impairment of the non-homologous end joining DNA repair pathway, specifically through mHTT-mediated Ku70 degradation. In the HD-iPSC-NPCs, we observed mHTT-Ku70 interaction, which promoted the ubiquitination of Ku70 protein and reduced Ku70-Ku80 heterodimer stability.

conclusionsThese finding suggest that ZIKV infection exacerbates a known HD-associated DNA damage phenotype, which is present in mHTT-expressing neurons. Our study therefore sheds new light on mechanisms underlying the interplay between ZIKV and HD, highlighting the relevance of viral infections on pathological progression in neurodegenerative disease.

Indexed as

DNA DamageDNA End-Joining RepairHuntingtin ProteinHuntington DiseaseInduced Pluripotent Stem CellsKu AutoantigenNeural Stem CellsZika VirusZika Virus InfectionCell DifferentiationHumansHTT protein, humanHuntingtin ProteinKu AutoantigenXrcc6 protein, humanDNA damageHuntington’s diseaseMutant huntingtinNHEJZika virus

Identifiers

PMID40770351
PMCPMC12329916

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LicenceCC BY-NC-ND
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.