Open AccessFibroblast Growth Factor 2 Enhances Zika Virus Infection in Human Fetal Brain
Author(s) -
Daniel Limonta,
Juan Jovel,
Anil Kumar,
Julia Lu,
Shangmei Hou,
Adriana M. Airo,
Joaquín López-Orozco,
Cheung Pang Wong,
Leina Saito,
William G. Branton,
Gane KaShu Wong,
Andrew L. Mason,
Christopher Power,
Tom C. Hobman
Publication year - 2019
Publication title -
the journal of infectious diseases (online. university of chicago press)/the journal of infectious diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.69
H-Index - 252
eISSN - 1537-6613
pISSN - 0022-1899
DOI - 10.1093/infdis/jiz073
Subject(s) - zika virus , microcephaly , biology , virology , fetus , viral replication , virus , immunology , fibroblast growth factor , interferon , pregnancy , genetics , receptor
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.