Jean-Pierre Levraud Team

NeuroInfection & Immunity

In brief

The team « NeuroInfection and Immunity » studies central nervous system infections, which are often lethal or cause severe neurological deficits in newborns. The host inflammatory response attacks microbes, but may also be highly deleterious to the brain. We use transparent zebrafish larva to visualize in real-time, by microscopy, bacteria or virus infected cells, as well as the immune response simultaneously.
The team, which is doubly affiliated to CNRS and Institut Pasteur, will establish itself in 2020 in the new Saclay building.

Our research

Our team is studying host-pathogen interactions during infections of the central nervous system (CNS), with the aim of improving the outcome of infectious encephalitis. We also have a broader interest in neuroinflammation in a wider context. We use the transparent zebrafish larva as our main model of study.
Main projects:
• Spatial dynamics of a neuroinvasive virus (such as Sindbis virus or Herpes Simplex Virus) and the interferon (IFN) response it elicits. Routes and rates of SINV entry in the brain and the spinal cord. Cell-to-cell propagation in the CNS. Cell types producing IFN, and responding to it, in the CNS. Impact of infection on survival and functions of neurons and other cells of the CNS.
• CNS repair after a viral infection. Development of recombinant viruses allowing controlled termination of infection. Identification of genes induced during the repair phase and comparison with sterile injury models. In vivo functional testing of common repair genes.
• Deconstructing the negative impact of IFN-mediated neuroinflammation. Description of the repertoire of ISGs (IFN-stimulated genes) in the different CNS cell types. CRISPR-based screen of individual ISG impact on brain development and function.
• Development of models of bacterial encephalitis/meningitis.

Selected Publications

LEVRAUD J.-P., Jouneau L., Briolat V., Laghi V., Boudinot P. IFN-stimulated genes in zebrafish and humans define an ancient arsenal of antiviral immunity. Journal of Immunology 203: 3361 (2019). DOI: 10.4049/jimmunol.1900804

• Hernández P.P., Strzelecka P.M., Athanasiadis E.I., Hall D., Robalo A.F., Collins C.M., Boudinot P., Cvejic A.*, LEVRAUD J.-P.* Single-cell transcriptional analysis reveals ILC-like cells in zebrafish. Science Immunology, 3:eaau5265 (2018). DOI: 10.1126/sciimmunol.aau5265

• Aguado L.C., Schmid S., May J., Sabin L.R., Panis M., Blanco-Melo D., Shim J.V., Sachs D., Cherry S., Simon A.E., LEVRAUD J.-P., tenOever B. RNase III nucleases from diverse kingdoms serve as antiviral effectors. Nature, 547:114 (2017). DOI: 10.1038/nature22990

• Passoni G., Langevin C., Palha N., Mounce B., Briolat V., Affaticati P., De Job E., Joly J.-S., Vignuzzi M., Saleh M.-C., Herbomel P., Boudinot P., LEVRAUD J.-P. Imaging of viral neuroinvasion in the zebrafish reveals that Sindbis and Chikungunya viruses favour different entry routes. Disease Models and Mechanisms, 10 :847 (2017). DOI: 10.1242/dmm.029231

• Mounce B.C., Poirier E.Z., Passoni G., Simon-Loriere E., Cesaro T., Prot M., Stapleford K.A., Moratorio G., Sakuntabhai A., LEVRAUD J.-P., M. Vignuzzi. Interferon-Induced Spermidine-Spermine Acetyltransferase and Polyamine Depletion Restrict Zika and Chikungunya Viruses. Cell Host & Microbe, 20 : 137-177 (2016). DOI: 10.1016/j.chom.2016.06.011

• Nguyen-Chi M., Laplace-Builhe B., Travnickova J., Luz-Crawford P., Tejedor G., Phan Q. T., Duroux-Richard I., LEVRAUD J-P., Kissa K, Lutfalla G., Jorgensen C., Djouad F. Identification of polarized macrophage subsets in zebrafish. eLife, 4:e07288 (2015). DOI: 10.7554/eLife.07288

• Kasher P.R., Jenkinson E.M., Briolat V., Gent D., Morrissey C., Zeef L.A., Rice G.I., LEVRAUD J.-P, Crow Y.J. Characterization of samhd1 morphant zebrafish recapitulates features of the human type I interferonopathy Aicardi-Goutières syndrome. Journal of Immunology 194:2819 (2015). DOI: 10.4049/jimmunol.1403157

LEVRAUD J.-P., Palha N., Langevin C., Boudinot P. Through the looking glass : witnessing host-virus interactions in zebrafish (review). Trends in Microbiology, 22 : 490-497 (2014). DOI: 10.1016/j.tim.2014.04.014

Team members

Team leader