Fibroblast Growth Factor 2 Enhances Zika Virus Infection in Human Fetal Brain

The Journal of Infectious Diseases
Daniel LimontaTom C Hobman

Abstract

Zika virus (ZIKV) is an emerging pathogen that can cause microcephaly and other neurological defects in developing fetuses. The cellular response to ZIKV in the fetal brain is not well understood. Here, we show that ZIKV infection of human fetal astrocytes (HFAs), the most abundant cell type in the brain, results in elevated expression and secretion of fibroblast growth factor 2 (FGF2). This cytokine was shown to enhance replication and spread of ZIKV in HFAs and human fetal brain explants. The proviral effect of FGF2 is likely mediated in part by suppression of the interferon response, which would represent a novel mechanism by which viruses antagonize host antiviral defenses. We posit that FGF2-enhanced virus replication in the fetal brain contributes to the neurodevelopmental disorders associated with in utero ZIKV infection. As such, targeting FGF2-dependent signaling should be explored further as a strategy to limit replication of ZIKV.

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Citations

Jul 18, 2019·Cells·Cheung Pang WongTom C Hobman
Jul 29, 2020·EMBO Molecular Medicine·Luigi MaddalunoSabine Werner
Sep 19, 2019·Science Signaling·Gholamreza Haqshenas, Christian Doerig
Aug 15, 2020·Frontiers in Microbiology·Quanshi LinPing Zhang
Jun 3, 2021·International Journal of Molecular Sciences·Oana-Stefana PurcaruAnica Dricu
May 19, 2021·Antimicrobial Agents and Chemotherapy·Daniel LimontaTom C Hobman

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