Axl Mediates ZIKA Virus Entry in Human Glial Cells and Modulates Innate Immune Responses
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ZIKA virus (ZIKV) is an emerging pathogen responsible for neurological disorders and congenital microcephaly. However, the molecular basis for ZIKV neurotropism remains poorly understood. Here, we show that Axl is expressed in human microglia and astrocytes in the developing brain and that it mediates ZIKV infection of glial cells. Axl-mediated ZIKV entry requires the Axl ligand Gas6, which bridges ZIKV particles to glial cells. Following binding, ZIKV is internalized through clathrin-mediated endocytosis and traffics to Rab5+ endosomes to establish productive infection. During entry, the ZIKV/Gas6 complex activates Axl kinase activity, which downmodulates interferon signaling and facilitates infection. ZIKV infection of human glial cells is inhibited by MYD1, an engineered Axl decoy receptor, and by the Axl kinase inhibitor R428. Our results highlight the dual role of Axl during ZIKV infection of glial cells: promoting viral entry and modulating innate immune responses. Therefore, inhibiting Axl function may represent a potential target for future antiviral therapies.
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AXL is a crucial receptor for infection of human glial cells (astrocytes and microglia) but not of human neural progenitor cells.
“another study reporting that AXL is a crucial receptor for infection of human glial cells (astrocytes and microglia) but not of human NPCs75.”
From The use of brain organoids to investigate neural development and disease (2017) · cites this paper as [75]
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- Authors
- Meertens, L., Labeau, A., Dejarnac, O., Cipriani, S., Sinigaglia, L., Bonnet-Madin, L., Le Charpentier, T., Hafirassou, M. L., Zamborlini, A., Cao-Lormeau, V.-M., Coulpier, M., Missé, D., Jouvenet, N., Tabibiazar, R., Gressens, P., Schwartz, O., & Amara, A.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Conservatoire National des Arts et Métiers (FR)
- École Nationale Vétérinaire d'Alfort (FR)
- Institut Pasteur (FR)
- Corresponding author
- Meertens, Laurent
- Amara, Ali
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2017-01
- Volume
- 18
- Issue
- 2
- Pages
- 324-333
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W2569913531
- Cited by
- 450
- References
- 46
- Citations by year
- 2026: 22 · 2025: 30 · 2024: 27 · 2023: 38 · 2022: 39 · 2021: 65 · 2020: 60 · 2019: 62 · 2018: 73 · 2017: 34
- FWCI
- 58.72
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- HAL (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Research Portal (King's College London) (submittedVersion, cc-by-nc-nd)
- Funders
- National Institutes of Health (R01 AI101400)
- Agence Nationale de la Recherche (ANR-10-IHUB-0002, CE14-0029)
- Institut Pasteur
- Horizon 2020 (734548)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Mosquito-borne diseases and control
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
- Keywords
- Zika virus, AXL receptor, Gas6, viral entry, glial cells, microglia, astrocytes, clathrin-mediated endocytosis, endosomes, interferon signaling, innate immunity, R428, neurotropism, antiviral therapy
- MeSH terms
- Zika Virus Infection, Zika Virus, Axl Receptor Tyrosine Kinase, Growth Arrest-Specific Protein 6, Brain, Clathrin, Endocytosis, Humans, Immunity, Innate, Interferon Type I, Neuroglia, Proto-Oncogene Proteins, Endosomes, Signal Transduction, Receptor Protein-Tyrosine Kinases, Intercellular Signaling Peptides and Proteins, Virus Internalization
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