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Cell Rep. 2016 Jun 14;15(11):2315-22. doi: 10.1016/j.celrep.2016.05.075. Epub 2016 Jun 3.

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

Author information

1
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Division of Infectious Disease, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
2
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
3
Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
4
Department of Psychiatry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
5
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: john.schoggins@utsouthwestern.edu.

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.

PMID:
27268504
PMCID:
PMC5645151
DOI:
10.1016/j.celrep.2016.05.075
[Indexed for MEDLINE]
Free PMC Article
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