A team led by Ali Amara, Inserm Research Director at Unit 944, “Pathology and Molecular Virology” (Inserm/CNRS/Paris Diderot University) describes, in an article published in Cell Reports, the mechanisms that allow Zika virus to infect the cells of the nervous system.
The ZIKAlliance project, coordinated by Inserm and funded under the Horizon 2020 programme of the European Commission’s Directorate-General for Research and Innovation, is aimed at characterising the fundamental and clinical aspects of infection by Zika virus, an emerging pathogen in America. The infection is generally mild, but the virus can also cause severe neurological diseases and congenital microcephaly in the foetus.
The researchers have shown that the Axl protein, which is expressed in numerous glial cells, facilitates entry of Zika virus into the brain. Entry of the virus into these cells requires a second protein, Gas6. The latter constitutes a mediator between the viral particles and glial cells.
The researchers also discovered that activation of the Axl protein lowers the immune response to Zika virus, thus promoting infection.
This study improves the state of knowledge of the molecular interactions that take place at the moment the virus enters the glial cells. These results represent a major step in understanding the neurological complications of the infection. Furthermore, they demonstrate in vitro that inhibition of the Axl pathway could represent a potential therapeutic target, although any side-effects associated with blocking it have yet to be identified.
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Axl mediates ZIKA virus entry in human glial cells and modulates innate immune responses Laurent Meertens 1, 2, 3 *, Athena Labeau 1, 2, 3, Ophelie Dejarnac 1, 2, 3, Sara Cipriani 4,,Laura Sinigaglia 5, Lucie Bonnet-Madin 1, 2 3, Tifenn Le Charpentier 4, Mohamed Lamine Hafirassou 1, 2, 3, Alessia Zamborlini 1, 2, 3, 6, Mai Cao-Lormeau 7, Muriel Coulpier 8, Dorothée Missé 9, Nolwenn Jouvenet 5, Ray Tabibiazar 10, Pierre Gressens 4, Olivier Schwartz 11 and Ali Amara 1, 2, 3 *1 INSERM U944,-CNRS 7212 Laboratoire de Pathologie et Virologie Moléculaire, Hôpital Saint-Louis 1 avenue Claude Vellefaux 75010, PARIS, France2 Institut Universitaire d'Hématologie, Hôpital Saint-Louis, 1 avenue Claude Vellefaux. 75010PARIS, France3 University Paris Diderot, Sorbonne Paris Cité, Hôpital St. Louis 1, Avenue Claude Vellefaux75475 Paris cedex 10 France4 PROTECT, INSERM, Université Paris Diderot, Sorbonne Paris Cité, F-75019 Paris, France5 UMR CNRS 3569, Viral Genomics and Vaccination Unit, Pasteur Institute, 75724 Paris, France6 Laboratoire PVM, Conservatoire des Arts et Metiers, 292 Rue Saint-Martin, 75003 Paris,France7 Institut Louis Malardé, Papeete, Tahiti, French Polynesia.8 ANSES, Université Paris-Est, Ecole Nationale Vétérinaire d’Alfort, UMR Virologie, Maisons-Alfort, France9 Laboratoire MIVEGEC, UMR 224 IRD/CNRS Montpellier, France10 Ruga Corporation, Two Houston Center, 909 Fannin St, #2000, Houston, TX 77010-101811 Unité Virus et Immunité, Institut Pasteur, 28 rue du Dr Roux, 75724 PARIS, France.Ce travail a reçu le soutien du NIH (Grant R01 N°AI101400), du programme de recherche et d'innovation Horizon 2020 de l'Union Européenne sous ZIKAlliance (grant agreement 734548), du Labex Integrative Biology of Emerging Infectious Diseases (IBEID), de l'agence ANR (bourse TIMTAMDEN).Cell Reports, 10 janvier 2017https://dx.doi.org/10.1016/j.celrep.2016.12.045