Axl mediates ZIKA virus entry in human glial cells and modulates innate immune responses - Université de Montpellier Accéder directement au contenu
Article Dans Une Revue Cell Reports Année : 2017

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

Van-Mai Cao-Lormeau
Muriel Coulpier
Nolwenn Jouvenet
Ray Tabibiazar
  • Fonction : Auteur
Olivier Schwartz
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Résumé

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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hal-02013511 , version 1 (11-02-2019)

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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, 2017, 18 (2), pp.324-333. ⟨10.1016/j.celrep.2016.12.045⟩. ⟨hal-02013511⟩
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