Western Zika Virus in Human Fetal Neural Progenitors Persists Long Term with Partial Cytopathic and Limited Immunogenic Effects

Natasha W. Hanners, Jennifer L. Eitson, Noriyoshi Usui, R. Blake Richardson, Eric M. Wexler, Genevieve Konopka, John W. Schoggins

Research output: Contribution to journalArticle

69 Scopus citations

Abstract

The recent Zika virus (ZIKV) outbreak in the Western hemisphere is associated with severe pathology in newborns, including microcephaly and brain damage. The mechanisms underlying these outcomes are under intense investigation. Here, we show that a 2015 ZIKV isolate replicates in multiple cell types, including primary human fetal neural progenitors (hNPs). In immortalized cells, ZIKV is cytopathic and grossly rearranges endoplasmic reticulum membranes similar to other flaviviruses. In hNPs, ZIKV infection has a partial cytopathic phase characterized by cell rounding, pyknosis, and activation of caspase 3. Despite notable cell death, ZIKV did not activate a cytokine response in hNPs. This lack of cell intrinsic immunity to ZIKV is consistent with our observation that virus replication persists in hNPs for at least 28 days. These findings, supported by published fetal neuropathology, establish a proof-of-concept that neural progenitors in the developing human fetus can be direct targets of detrimental ZIKV-induced pathology.

Original languageEnglish (US)
Pages (from-to)2315-2322
Number of pages8
JournalCell Reports
Volume15
Issue number11
DOIs
StatePublished - Jun 14 2016

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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