{"doi":"10.1101/2024.09.27.615512","title":"The Human Neural Cell Atlas of Zika Infection in developing human brain tissue: viral pathogenesis, innate immunity, and lineage reprogramming","abstract":"Zika virus (ZIKV) infection during pregnancy can lead to fetal brain infection and developmental anomalies collectively known as congenital Zika syndrome (CZS). To define the molecular features underlying CZS in a relevant human cell model, we evaluated ZIKV infection and neurodevelopment in primary fetal brain explants and induced pluripotent stem cell-derived mixed neural cultures at single cell resolution. We identified astrocytes as key innate immune sentinel cells detecting ZIKV and producing IFN-β. In contrast, neural progenitor cells displayed impaired innate immunity and supported high levels of viral replication. ZIKV infection of neurons suppressed differentiation and synaptic signaling networks and programmed a molecular switch from neurogenesis to astrogliogenesis. We identified a universal ZIKV-driven cellular stress response linked to intrinsic apoptosis and regulated by IFN-β. These findings reveal how innate immune signaling intersects with ZIKV-driven perturbations in cellular function to influence CZS outcomes including neuron developmental dysfunction and apoptotic cell death.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":504085,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.5747,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":633034,"name":"Leanne S. Whitmore","orcid":"0000-0002-8721-8701","position":1,"is_corresponding":false},{"id":1336818,"name":"Dante Moreno","orcid":null,"position":2,"is_corresponding":false},{"id":1104126,"name":"Karan Malhotra","orcid":"0000-0001-7589-5310","position":3,"is_corresponding":false},{"id":547197,"name":"Jennifer Tisoncik-Go","orcid":"0000-0003-1381-265X","position":4,"is_corresponding":false},{"id":1100071,"name":"Emily Tran","orcid":null,"position":5,"is_corresponding":false},{"id":1354649,"name":"Nick Wren","orcid":null,"position":6,"is_corresponding":false},{"id":104361,"name":"Ian A. Glass","orcid":"0000-0001-6762-8407","position":7,"is_corresponding":false},{"id":250244,"name":"Jessica E. Young","orcid":"0000-0003-2106-0339","position":8,"is_corresponding":false},{"id":108916,"name":"Michael Gale","orcid":"0000-0002-6332-7436","position":9,"is_corresponding":false},{"id":108910,"name":"Caleb Stokes","orcid":"0000-0003-3741-0057","position":0,"is_corresponding":true}],"reference_count":82,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:10:35.597333Z","pmid":"39386476","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":[]}