Evidence map›Paper›PMID 39765020›Full record

ArticleVirology2025

The Zika virus NS5 protein binds HSP90 to suppress EGF-induced Akt signaling and trophoblast cell migration.

Nika Hajari, Megan Knoll, Amy Lu, Isaac Barber-Axthelm, Michael Gale

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

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

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Nika HajariDepartment of Immunology, Center for Innate Immunity and Immune Disease, School of Medicine, University of Washington, Seattle, USA; Department of Global Health, University of Washington, Seattle, WA, USA.
Megan KnollDepartment of Immunology, Center for Innate Immunity and Immune Disease, School of Medicine, University of Washington, Seattle, USA.
Amy LuDepartment of Immunology, Center for Innate Immunity and Immune Disease, School of Medicine, University of Washington, Seattle, USA; Department of Global Health, University of Washington, Seattle, WA, USA.
Isaac Barber-AxthelmDepartment of Comparative Medicine, University of Washington, Seattle, WA, USA.
Michael GaleDepartment of Immunology, Center for Innate Immunity and Immune Disease, School of Medicine, University of Washington, Seattle, USA; Department of Global Health, University of Washington, Seattle, WA, USA; Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN, USA; Institute on Infectious Diseases, University of Minnesota, Minneapolis, MN, USA. Electronic address: mgale@umn.edu.

Funding

Washington National Primate Research CenterP51OD010425 · OD · UNIVERSITY OF WASHINGTON · PI Mari Ostendorf · 2012 to 2026
$201.8M
JAK-STAT Control of Zika Virus-Induced Fetal InjuryR01AI143265 · NIAID · UNIVERSITY OF WASHINGTON · PI ADAMS WALDORF, KRISTINA M., GALE, MICHAEL · 2019 to 2023
$4.6M
Innate Immune Regulation of Zika Virus InfectionR01AI145296 · NIAID · UNIVERSITY OF WASHINGTON · PI COYNE, CAROLYN B, DIAMOND, MICHAEL S · 2019 to 2023
$4.1M
Innate Immunity to West Nile VirusR01AI179722 · NIAID · UNIVERSITY OF WASHINGTON · PI Michael Gale, Andrew Atwell Oberst · 2024 to 2026
$2.6M
Innate Immune Mechanisms Controlling Flavivirus NeurovirulenceR01AI183793 · NIAID · UNIVERSITY OF MINNESOTA · PI Michael Gale, Andrew Atwell Oberst · 2024 to 2026
$2.4M
NIAID NIH HHS R01 AI143265NIAID NIH HHS R01 AI145296NIAID NIH HHS R01 AI179722NIAID NIH HHS R01 AI183793NIH HHS P51 OD010425
6 · The paper itself

Abstract

Zika virus (ZIKV) infection during pregnancy can cause congenital Zika virus syndrome (CZV), including fetal growth restriction and death. In the developing placenta, trophoblast cells respond to epidermal growth factor (EGF) to migrate into the decidua to facilitate implantation and fetal development. EGF activates the Akt protein kinase, a master regulator of trophoblast cell migration. Akt signaling and stability are dependent on heat shock protein 90 (HSP90), which mediates the maturation of proteins necessary for EGF/Akt signaling. Here we show that ZIKV infection inhibits EGF-mediated Akt activation and downstream signaling to suppress trophoblast migration. The ZIKV non-structural protein 5 (NS5) is sufficient to inhibit trophoblast migration through its binding interaction with HSP90, leading to suppression of Akt phosphorylation and inhibition of EGF-induced trophoblast migration. Thus, ZIKV NS5/HSP90 interactions play a key role in disruption of trophoblast function, revealing an underlying cause of improper placental development and fetal disease.

Indexed as

Cell MovementEpidermal Growth FactorHSP90 Heat-Shock ProteinsProto-Oncogene Proteins c-aktTrophoblastsViral Nonstructural ProteinsZika VirusZika Virus InfectionCell LineFemaleHumansPhosphorylationPregnancyProtein BindingSignal TransductionEpidermal Growth FactorHSP90 Heat-Shock ProteinsNS5 protein, flavivirusProto-Oncogene Proteins c-aktViral Nonstructural ProteinsAktEGFHSP90MigrationNonstructural protein 5 (NS5)PI3KPlacentaPregnancyTrophoblastZika virus (ZIKV)

Identifiers

PMID39765020
PMCPMC11832110

What OpenQuestion holds

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Registered trials

None linked

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.