Axl Mediates ZIKA Virus Entry in Human Glial Cells and Modulates Innate Immune Responses.

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.

DOI: 10.1016/j.celrep.2016.12.045

Cite this paper

@article{Meertens2017AxlMZ, title={Axl Mediates ZIKA Virus Entry in Human Glial Cells and Modulates Innate Immune Responses.}, author={Laurent Meertens and Athena Labeau and Oph{\'e}lie Dejarnac and Sara Cipriani and Laura Sinigaglia and Lucie Bonnet-Madin and Tifenn le Charpentier and Mohamed Lamine Hafirassou and Alessia Zamborlini and Van-Mai Cao-Lormeau and Muriel Coulpier and Doroth{\'e}e Miss{\'e} and Nolwenn Jouvenet and Ray Tabibiazar and Pierre Gressens and Olivier Schwartz and Ali Amara}, journal={Cell reports}, year={2017}, volume={18 2}, pages={324-333} }