{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:43:49Z","timestamp":1790768629830,"version":"4.1.0"},"reference-count":66,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,29]],"date-time":"2022-12-29T00:00:00Z","timestamp":1672272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Pasteur\u2013Paris University (PPU) International PhD Program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Rabies is caused by neurotropic rabies virus (RABV), contributing to 60,000 human deaths annually. Even though rabies leads to major public health concerns worldwide, we still do not fully understand factors determining RABV tropism and why glial cells are unable to clear RABV from the infected brain. Here, we compare susceptibilities and immune responses of CNS cell types to infection with two RABV strains, Tha and its attenuated variant Th2P-4M, mutated on phospho- (P-protein) and matrix protein (M-protein). We demonstrate that RABV replicates in human stem cell-derived neurons and astrocytes but fails to infect human iPSC-derived microglia. Additionally, we observed major differences in transcription profiles and quantification of intracellular protein levels between antiviral immune responses mediated by neurons, astrocytes (IFNB1, CCL5, CXCL10, IL1B, IL6, and LIF), and microglia (CCL5, CXCL10, ISG15, MX1, and IL6) upon Tha infection. We also show that P- and M-proteins of Tha mediate evasion of NF-\u03baB- and JAK-STAT-controlled antiviral host responses in neuronal cell types in contrast to glial cells, potentially explaining the strong neuron-specific tropism of RABV. Further, Tha-infected astrocytes and microglia protect neurons from Tha infection via a filtrable and transferable agent. Overall, our study provides novel insights into RABV tropism, showing the interest in studying the interplay of CNS cell types during RABV infection.<\/jats:p>","DOI":"10.3390\/v15010088","type":"journal-article","created":{"date-parts":[[2022,12,29]],"date-time":"2022-12-29T02:59:01Z","timestamp":1672282741000},"page":"88","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Susceptibilities of CNS Cells towards Rabies Virus Infection Is Linked to Cellular Innate Immune Responses"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2922-6057","authenticated-orcid":false,"given":"Lena","family":"Feige","sequence":"first","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 de Paris, Lyssavirus Epidemiology and Neuropathology, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Kozaki","sequence":"additional","affiliation":[{"name":"Singapore Immunology Network, Agency for Science, Technology and Research, 8A Biomedical Grove, Immunos Building, Level 3, Singapore 138648, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0747-7760","authenticated-orcid":false,"given":"Guilherme","family":"Dias de Melo","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 de Paris, Lyssavirus Epidemiology and Neuropathology, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Guillemot","sequence":"additional","affiliation":[{"name":"Hub de Bioinformatique et Biostatistique, D\u00e9partement Biologie Computationnelle, Institut Pasteur, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0881-4263","authenticated-orcid":false,"given":"Florence","family":"Larrous","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 de Paris, Lyssavirus Epidemiology and Neuropathology, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florent","family":"Ginhoux","sequence":"additional","affiliation":[{"name":"Singapore Immunology Network, Agency for Science, Technology and Research, 8A Biomedical Grove, Immunos Building, Level 3, Singapore 138648, Singapore"},{"name":"Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai 200025, China"},{"name":"Translational Immunology Institute, SingHealth Duke-NUS Academic Medical Center, 20 College Road, Discovery Tower Level 8, Singapore 169856, Singapore"},{"name":"Inserm U1015, Gustave Roussy, B\u00e2timent de M\u00e9decine Mol\u00e9culaire, 114 Rue Edouard Vaillant, 94800 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2608-5589","authenticated-orcid":false,"given":"Herv\u00e9","family":"Bourhy","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 de Paris, Lyssavirus Epidemiology and Neuropathology, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1016\/S0140-6736(13)62707-5","article-title":"Current status of rabies and prospects for elimination","volume":"384","author":"Fooks","year":"2014","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"17091","DOI":"10.1038\/nrdp.2017.91","article-title":"Rabies","volume":"3","author":"Fooks","year":"2017","journal-title":"Nat. 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