ArticleNature neuroscience2018
Stress-induced unfolded protein response contributes to Zika virus-associated microcephaly.
Article in Nature neuroscience, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
104 citing papers in PubMed, 1 synthesis or guideline pooled it, 150 citations in OpenAlex.
- Neuroprotective and reparative effects of endoplasmic reticulum luminal proteins - mesencephalic astrocyte-derived neurotrophic factor and cerebral dopamine neurotrophic factor.Croatian medical journal · 2019Pooled it
- Review
- Oropouche virus causes severe congenital disease in embryonic mice.Nature communications · 2026Article
- Cellular Responses to Flavivirus Infections: Stress Signaling at the Crossroads of Host Defense and Virus Infection.Viruses · 2026Review
- New developments and applications of human organoids.Nature reviews. Molecular cell biology · 2026Review
- Cdk7 promotes neuritogenesis in cortical neurons and contributes to social behavior in mice.Cellular and molecular life sciences : CMLS · 2026Article
- Comparative analysis of placental transmission mechanisms for Dengue and Zika viruses: outcomes and future directions.Frontiers in immunology · 2026Review
- Zika virus and host innate immunity: mechanisms of activation and evasion.Frontiers in immunology · 2026Review
- Metabolic functions for molecular chaperones and stress proteins in microcephaly.Cellular and molecular life sciences : CMLS · 2025Review
- Activation of PD-1/PD-L1 immune checkpoint by Zika virus.PLoS pathogens · 2025Article
- Article
- Zika virus non-structural protein NS2A mediated endoplasmic reticulum stress through interacting with Sarco/endoplasmic reticulum CaJournal of virology · 2025Article
- Bi-allelic variants in TM2D3 cause a severe syndromic neurodevelopmental disorder associated with endoplasmic reticulum and mitochondrial abnormalities.American journal of human genetics · 2025Article
- The human neural cell atlas of Zika virus infection in developing brain tissue.Cell reports. Medicine · 2025Article
- Congenital Zika virus infection in laboratory animals: a comparative review highlights translational studies on the maternal-foetal interface.Memorias do Instituto Oswaldo Cruz · 2025Review
- Epidemic Zika virus strains from the Asian lineage induce an attenuated fetal brain pathogenicity.Nature communications · 2024Article
- An Overview of Zika Virus and Zika Virus Induced Neuropathies.International journal of molecular sciences · 2024Review
- Erp57 facilitates ZIKV-induced DNA damage via NS2B/NS3 complex formation.Emerging microbes & infections · 2024Article
- PIGK defects induce apoptosis in Purkinje cells and acceleration of neuroectodermal differentiation.Cell death & disease · 2024Article
- Activation of ATF3 via the integrated stress response pathway regulates innate immune response to restrict Zika virus.Journal of virology · 2024Article
44 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Accumulating evidence support a causal link between Zika virus (ZIKV) infection during gestation and congenital microcephaly. However, the mechanism of ZIKV-associated microcephaly remains unclear. We combined analyses of ZIKV-infected human fetuses, cultured human neural stem cells and mouse embryos to understand how ZIKV induces microcephaly. We show that ZIKV triggers endoplasmic reticulum stress and unfolded protein response in the cerebral cortex of infected postmortem human fetuses as well as in cultured human neural stem cells. After intracerebral and intraplacental inoculation of ZIKV in mouse embryos, we show that it triggers endoplasmic reticulum stress in embryonic brains in vivo. This perturbs a physiological unfolded protein response within cortical progenitors that controls neurogenesis. Thus, ZIKV-infected progenitors generate fewer projection neurons that eventually settle in the cerebral cortex, whereupon sustained endoplasmic reticulum stress leads to apoptosis. Furthermore, we demonstrate that administration of pharmacological inhibitors of unfolded protein response counteracts these pathophysiological mechanisms and prevents microcephaly in ZIKV-infected mouse embryos. Such defects are specific to ZIKV, as they are not observed upon intraplacental injection of other related flaviviruses in mice.
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Registered trials
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 OpenQuestion graph.