ArticleJournal of virology2019
High-Throughput Screening Identifies Mixed-Lineage Kinase 3 as a Key Host Regulatory Factor in Zika Virus Infection.
Article in Journal of virology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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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
11 citing papers in PubMed, 25 citations in OpenAlex.
- Multi-omics analysis reveals key immunogenic signatures induced by oncolytic Zika virus infection of paediatric brain tumour cells.Scientific reports · 2025Article
- Amuvatinib Blocks SARS-CoV-2 Infection at the Entry Step of the Viral Life Cycle.Microbiology spectrum · 2023Article
- A platform of assays for the discovery of anti-Zika small-molecules with activity in a 3D-bioprinted outer-blood-retina model.PloS one · 2022Article
- Review
- Hepatitis B virus-host interactions and novel targets for viral cure.Current opinion in virology · 2021Review
- Zika Virus Pathogenesis: A Battle for Immune Evasion.Vaccines · 2021Review
- The regulatory function of mixed lineage kinase 3 in tumor and host immunity.Pharmacology & therapeutics · 2021Review
- Zika virus infection induces endoplasmic reticulum stress and apoptosis in placental trophoblasts.Cell death discovery · 2021Article
- Identification of an Antiviral Compound from the Pandemic Response Box that Efficiently Inhibits SARS-CoV-2 Infection In Vitro.Microorganisms · 2020Article
- Pyroptosis and ferroptosis induced by mixed lineage kinase 3 (MLK3) signaling in cardiomyocytes are essential for myocardial fibrosis in response to pressure overload.Cell death & disease · 2020Article
- ANKS4B Restricts Replication of Zika Virus by Downregulating the Autophagy.Frontiers in microbiology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Zika virus (ZIKV) life cycle involves multiple steps and requires interactions with host factors. However, the inability to systematically identify host regulatory factors for ZIKV has hampered antiviral development and our understanding of pathogenicity. Here, using a bioactive compound library with 2,659 small molecules, we applied a high-throughput and imaging-based screen to identify host factors that modulate ZIKV infection. The screen yielded hundreds of hits that markedly inhibited or potentiated ZIKV infection in SNB-19 glioblastoma cells. Among the hits, URMC-099, a mixed-lineage kinase 3 (MLK3) inhibitor, significantly facilitated ZIKV replication in both SNB-19 cells and the neonatal mouse brain. Using gene silencing and overexpression, we further confirmed that MLK3 was a host restriction factor against ZIKV. Mechanistically, MLK3 negatively regulated ZIKV replication through induction of the inflammatory cytokines interleukin-6 (IL-6), IL-8, tumor necrosis factor alpha (TNF-α), and monocyte chemoattractant protein 1 (MCP-1) but did not modulate host interferon-related pathways. Importantly, ZIKV activated the MLK3/MKK7/Jun N-terminal protein kinase (JNK) pathway in both SNB-19 cells and neonatal mouse brain. Together, these findings reveal a critical role for MLK3 in regulating ZIKV infection and facilitate the development of anti-ZIKV therapeutics by providing a number of screening hits.
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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.