Skip to Main content Skip to Navigation
Journal articles

Axl mediates ZIKA virus entry in human glial cells and modulates innate immune responses

Laurent Meertens 1, 2 Athena Labeau 1, 2 Ophélie Dejarnac 1, 2 Sara Cipriani 3 Laura Sinigaglia 4 Lucie Bonnet-Madin 1, 2 Tifenn Le Charpentier 3 Mohamed Hafirassou 1, 2 Alessia Zamborlini 1, 2, 5 Van-Mai Cao-Lormeau 6 Muriel Coulpier 7 Dorothée Missé 8 Nolwenn Jouvenet 4 Ray Tabibiazar 9 Pierre Gressens 3 Olivier Schwartz 10 Ali Amara 1, 2
1 PVM (UMR_7151) - Pathologie et virologie moléculaire
2 Institut Universitaire d'Hématologie [Hôpital Saint-Louis - APHP]
3 PROTECT - Neuroprotection du Cerveau en Développement / Promoting Research Oriented Towards Early Cns Therapies
4 Génomique virale et vaccination
5 CNAM - Conservatoire National des Arts et Métiers [CNAM]
6 Emerging Infectious Diseases
7 VIRO - Virologie UMR1161
8 MIVEGEC - Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle
9 Ruga Corporation
10 Virus et Immunité
Abstract : 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.
Document type :
Journal articles
Complete list of metadatas

Cited literature [44 references]  Display  Hide  Download
https://hal.umontpellier.fr/hal-02013511
Contributor : Hal Mivegec <>
Submitted on : Monday, February 11, 2019 - 9:53:43 AM
Last modification on : Tuesday, December 8, 2020 - 9:45:00 AM
Long-term archiving on: : Sunday, May 12, 2019 - 12:44:20 PM

File

Vignette du document
PIIS2211124716317521.pdf
Publisher files allowed on an open archive

Licence

Distributed under a Creative Commons Attribution 4.0 International License

Identifiers

Collections

UNIV-MONTPELLIER | CNRS | UNIV-PARIS7 | INRA | ANSES | AGROPOLIS | USPC | IRD | B3ESTE | PASTEUR | CNAM | UNIV-HESAM | INRAE | UNIV-PARIS

Citation

Laurent Meertens, Athena Labeau, Ophélie Dejarnac, Sara Cipriani, Laura Sinigaglia, et al.. Axl mediates ZIKA virus entry in human glial cells and modulates innate immune responses. Cell Reports, Elsevier Inc, 2017, 18 (2), pp.324-333. ⟨10.1016/j.celrep.2016.12.045⟩. ⟨hal-02013511⟩

Export

BibTeX TEI DC DCterms EndNote

Share

Metrics

Record views

457

Files downloads

940