{"doi":"10.1016/j.celrep.2025.116159","title":"Human brain cell types shape host-rabies virus transcriptional interactions revealing a preexisting pro-viral astrocyte subpopulation","abstract":"How virus-host cell interactions and innate immune antagonism shape neurotropic infection dynamics across diverse brain cell types is largely unknown. To \"unmask\" and study how innate immune inhibition affects cell-type-specific transcriptional regulation of the human and viral genome, we perform single-cell RNA sequencing of human brain cell co-cultures, comparing an isolate of rabies virus (RABV) to its mutant incapable of antagonizing interferon- and nuclear factor (NF)-κB-dependent responses. RABV gene expression is shaped by host cell type. RABV induces small-scale, cell-type-conserved transcriptional programs that likely support infection by (1) hijacking negative transcriptional feedback of pro-viral factors while (2) reducing anti-viral RNAs. Unexpectedly, disinhibited innate immune signaling increases RABV transcription, most strikingly in an infection-independent \"pro-viral\" astrocyte subpopulation. Further analysis suggests that pro-viral-like astrocytes are a rare subtype in the human brain and are primed to protect the brain during viral infection in concert with interferon-sensitive microglia recalcitrant to infection.","journal":"Cell Reports","year":2025,"id":526649,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8976,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":853410,"name":"Karl Young","orcid":"0000-0001-9126-5810","position":1,"is_corresponding":false},{"id":1402200,"name":"Juan‐Pablo Cerapio","orcid":"0000-0002-3032-3180","position":2,"is_corresponding":false},{"id":1402201,"name":"Tatsuya Kozaki","orcid":"0000-0003-4997-3199","position":3,"is_corresponding":false},{"id":841617,"name":"Lauriane Kergoat","orcid":"0000-0002-5609-4398","position":4,"is_corresponding":false},{"id":844012,"name":"Valentina Libri","orcid":"0000-0002-2080-1089","position":5,"is_corresponding":false},{"id":71133,"name":"Florent Ginhoux","orcid":"0000-0002-2857-7755","position":6,"is_corresponding":false},{"id":844011,"name":"Milena Hasan","orcid":"0000-0002-0879-7099","position":7,"is_corresponding":false},{"id":692929,"name":"Lamya Ben Ameur","orcid":null,"position":8,"is_corresponding":false},{"id":383189,"name":"Gregory Chin","orcid":"0000-0001-7805-7240","position":9,"is_corresponding":false},{"id":785493,"name":"Zach Goode","orcid":null,"position":10,"is_corresponding":false},{"id":841618,"name":"Hervé Bourhy","orcid":"0000-0002-2608-5589","position":11,"is_corresponding":false},{"id":573984,"name":"Arpiar Saunders","orcid":"0000-0001-7540-7452","position":12,"is_corresponding":false},{"id":1402199,"name":"Lena Feige","orcid":"0000-0003-2922-6057","position":0,"is_corresponding":true}],"reference_count":118,"raw_metadata":null,"created_at":"2026-07-19T02:50:30.402772Z","pmid":"40864551","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}