ArticlePLoS pathogens2020
Peli1 signaling blockade attenuates congenital zika syndrome.
Article in PLoS pathogens, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Mapping the Cerebral Organoid Landscape: A Systematic Review of Preclinical 3D Models in Neuroscience.Advanced healthcare materials · 2026Pooled it
- Regulation of placental development and function by ubiquitination.Molecular medicine (Cambridge, Mass.) · 2025Review
- Innate immune sensing and vaccine strategies against West Nile virus: role of Toll-like receptors and viral evasion mechanisms.Frontiers in microbiology · 2025Review
- RNA-Seq Reveals Transcriptome Changes Following Zika Virus Infection in Fetal Brains inViruses · 2024Article
- ZIKV induces P62-mediated autophagic degradation of TRAF6 through TRAF6-NS1 interaction.iScience · 2024Article
- c-FLIP facilitates ZIKV infection by mediating caspase-8/3-dependent apoptosis.PLoS pathogens · 2024Article
- Role of microglia in brain development after viral infection.Frontiers in cell and developmental biology · 2024Review
- Pellino 3 promotes the colitis-associated colorectal cancer through suppression of IRF4-mediated negative regulation of TLR4 signalling.Molecular oncology · 2023Article
- Pellino Proteins in Viral Immunity and Pathogenesis.Viruses · 2023Review
- Viral Protein Accumulation of Zika Virus Variants Links with Regulation of Innate Immunity for Differential Control of Viral Replication, Spread, and Response to Interferon.Journal of virology · 2023Article
- Pellino1 Restricts Herpes Simplex Virus Infections in the Epidermis and Dissemination to Sebaceous Glands.The Journal of investigative dermatology · 2023Article
- Pathogenesis of Zika Virus Infection.Annual review of pathology · 2023Review
- Biology of Pellino1: a potential therapeutic target for inflammation in diseases and cancers.Frontiers in immunology · 2023Review
- Gain-of-function genetic screening identifies the antiviral function of TMEM120A via STING activation.Nature communications · 2022Article
- Maternal Inflammation Exaggerates Offspring Susceptibility to Cerebral Ischemia-Reperfusion Injury via the COX-2/PGD2/DPOxidative medicine and cellular longevity · 2022Article
- The Emerging Roles of Pellino Family in Pattern Recognition Receptor Signaling.Frontiers in immunology · 2022Review
- Dendritic Cell-Specific Role for Pellino2 as a Mediator of TLR9 Signaling Pathway.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- The roles of microglia in viral encephalitis: from sensome to therapeutic targeting.Cellular & molecular immunology · 2021Review
Corrections and comments
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Authors and funding
24 authors at 2 institutions in 1 country.
Funding
Abstract
Zika virus (ZIKV) infects pregnant women and causes devastating congenital zika syndrome (CZS). How the virus is vertically transmitted to the fetus and induces neuronal loss remains unclear. We previously reported that Pellino (Peli)1, an E3 ubiquitin ligase, promotes p38MAPK activation in microglia and induction of lethal encephalitis by facilitating the replication of West Nile virus (WNV), a closely related flavivirus. Here, we found that Peli1 expression was induced on ZIKV-infected human monocytic cells, peripheral blood mononuclear cells, human first-trimester placental trophoblasts, and neural stem cell (hNSC)s. Peli1 mediates ZIKV cell attachment, entry and viral translation and its expression is confined to the endoplasmic reticulum. Moreover, Peli1 mediated inflammatory cytokine and chemokine responses and induced cell death in placental trophoblasts and hNSCs. ZIKV-infected pregnant mice lacking Peli1 signaling had reduced placental inflammation and tissue damage, which resulted in attenuated congenital abnormalities. Smaducin-6, a membrane-tethered Smad6-derived peptide, blocked Peli1-mediated NF-κB activation but did not have direct effects on ZIKV infection. Smaducin-6 reduced inflammatory responses and cell death in placental trophoblasts and hNSCs, and diminished placental inflammation and damage, leading to attenuated congenital malformations in mice. Collectively, our results reveal a novel role of Peli1 in flavivirus pathogenesis and suggest that Peli1 promotes ZIKV vertical transmission and neuronal loss by mediating inflammatory cytokine responses and induction of cell death. Our results also identify Smaducin-6 as a potential therapeutic candidate for treatment of CZS.
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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.