ArticleProceedings of the National Academy of Sciences of the United States of America2017
AXL-dependent infection of human fetal endothelial cells distinguishes Zika virus from other pathogenic flaviviruses.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 137 papers.
What it found
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Who cites it
137 citing papers in PubMed, 209 citations in OpenAlex.
- Review
- Vertical Transmission of Zika Virus: The Immune-Pathophysiological Interface of the Placenta.Journal of immunology research · 2026Review
- Zika virus and host protein interactions for understanding molecular mechanisms of pathogenesis and therapeutic development.Frontiers in cellular and infection microbiology · 2026Review
- Zika virus and the fetal-maternal interface: deciphering the mechanisms of placental infection and implications for pregnancy outcomes.Emerging microbes & infections · 2025Review
- Review
- Variation in virion phosphatidylserine content drives differential GAS6 binding among closely related flaviviruses.Journal of virology · 2025Article
- Molecular mechanisms of SARS-CoV-2 entry: implications for biomedical strategies.Microbiology and molecular biology reviews : MMBR · 2025Review
- SFTSV utilizes AXL/GAS6 for entry via PI3K-PLC-dependent macropinocytosis activated by AXL-kinase.Journal of virology · 2025Article
- Review
- Autophagy-mediated downregulation of AXL and TIM-1 promotes sustained Zika virus infection.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A single mutation in the PrM gene of Zika virus determines AXL dependency for infection of human neural cells.Journal of virology · 2025Article
- Persistent innate immune dysfunction and ZIKV replication in the gastrointestinal tract during SIV infection in pigtail macaques.Frontiers in immunology · 2025Article
- The placental battlefield: viral strategies and immune countermeasures.Frontiers in immunology · 2025Review
- Insights into mosquito-borne arbovirus receptors.Cell insight · 2024Review
- The ability of human TIM1 to bind phosphatidylethanolamine enhances viral uptake and efferocytosis compared to rhesus and mouse orthologs.Journal of virology · 2024Article
- Chronic innate immune impairment and ZIKV persistence in the gastrointestinal tract during SIV infection in pigtail macaques.bioRxiv : the preprint server for biology · 2024Article
- The Raf kinase inhibitors Dabrafenib and Regorafenib impair Zika virus replication via distinct mechanisms.Journal of virology · 2024Article
- The ability of human TIM1 to bind phosphatidylethanolamine enhances viral uptake and efferocytosis compared to rhesus and mouse orthologs.bioRxiv : the preprint server for biology · 2024Article
- Zika Virus Neuropathogenesis-Research and Understanding.Pathogens (Basel, Switzerland) · 2024Review
- Repurposing of Zika virus live-attenuated vaccine (ZIKV-LAV) strains as oncolytic viruses targeting human glioblastoma multiforme cells.Journal of translational medicine · 2024Article
77 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Although a causal relationship between Zika virus (ZIKV) and microcephaly has been established, it remains unclear why ZIKV, but not other pathogenic flaviviruses, causes congenital defects. Here we show that when viruses are produced in mammalian cells, ZIKV, but not the closely related dengue virus (DENV) or West Nile virus (WNV), can efficiently infect key placental barrier cells that directly contact the fetal bloodstream. We show that AXL, a receptor tyrosine kinase, is the primary ZIKV entry cofactor on human umbilical vein endothelial cells (HUVECs), and that ZIKV uses AXL with much greater efficiency than does DENV or WNV. Consistent with this observation, only ZIKV, but not WNV or DENV, bound the AXL ligand Gas6. In comparison, when DENV and WNV were produced in insect cells, they also infected HUVECs in an AXL-dependent manner. Our data suggest that ZIKV, when produced from mammalian cells, infects fetal endothelial cells much more efficiently than other pathogenic flaviviruses because it binds Gas6 more avidly, which in turn facilitates its interaction with AXL.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.