Genetic Ablation of AXL Does Not Protect Human Neural Progenitor Cells and Cerebral Organoids from Zika Virus Infection
Open accessAbstract
Zika virus (ZIKV) can cross the placental barrier, resulting in infection of the fetal brain and neurological defects including microcephaly. The cellular tropism of ZIKV and the identity of attachment factors used by the virus to gain access to key cell types involved in pathogenesis are under intense investigation. Initial studies suggested that ZIKV preferentially targets neural progenitor cells (NPCs), providing an explanation for the developmental phenotypes observed in some pregnancies. The AXL protein has been nominated as a key attachment factor for ZIKV in several cell types including NPCs. However, here we show that genetic ablation of AXL has no effect on ZIKV entry or ZIKV-mediated cell death in human induced pluripotent stem cell (iPSC)-derived NPCs or cerebral organoids. These findings call into question the utility of AXL inhibitors for preventing birth defects after infection and suggest that further studies of viral attachment factors in NPCs are needed.
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- Authors
- Wells, M. F., Salick, M. R., Wiskow, O., Ho, D. J., Worringer, K. A., Ihry, R. J., Kommineni, S., Bilican, B., Klim, J. R., Hill, E. J., Kane, L. T., Ye, C., Kaykas, A., & Eggan, K.
- Affiliations
- Broad Institute (US)
- Harvard University (US)
- Corresponding author
- Kaykas, Ajamete
- Eggan, Kevin
- ORCID
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2016-12
- Volume
- 19
- Issue
- 6
- Pages
- 703-708
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- OpenAlex
- W2559721763
- Cited by
- 269
- References
- 24
- Citations by year
- 2026: 9 · 2025: 12 · 2024: 14 · 2023: 13 · 2022: 20 · 2021: 44 · 2020: 27 · 2019: 40 · 2018: 49 · 2017: 40 · 2016: 1
- FWCI
- 42.72
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- The Novartis Repository (Novartis) (submittedVersion)
- Funders
- Stanley Center for Psychiatric Research
- Harvard Stem Cell Institute
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Mosquito-borne diseases and control
- Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Viral Infections and Immunology Research
- Keywords
- Zika virus, AXL receptor, neural progenitor cells, brain organoids, viral entry, cell death, microcephaly, placental barrier, iPSC-derived neural progenitor cells, AXL inhibitor, congenital malformations
- MeSH terms
- Neuroprotection, Zika Virus Infection, Axl Receptor Tyrosine Kinase, Humans, Organoids, Proto-Oncogene Proteins, Cell Death, Gene Deletion, Receptor Protein-Tyrosine Kinases, Cerebrum, Gene Knockout Techniques, Neural Stem Cells
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