{"doi":"10.1101/2023.10.25.563950","title":"Dysregulated neuroimmune interactions and sustained type I interferon signaling after human immunodeficiency virus type 1 infection of human iPSC derived microglia and cerebral organoids","abstract":"ABSTRACT Human immunodeficiency virus type-1 (HIV-1) associated neurocognitive disorder (HAND) affects up to half of HIV-1 positive patients with long term neurological consequences, including dementia. There are no effective therapeutics for HAND because the pathophysiology of HIV-1 induced glial and neuronal functional deficits in humans remains enigmatic. To bridge this knowledge gap, we established a model simulating HIV-1 infection in the central nervous system using human induced pluripotent stem cell (iPSC) derived microglia combined with sliced neocortical organoids. Upon incubation with two replication-competent macrophage-tropic HIV-1 strains (JRFL and YU2), we observed that microglia not only became productively infected but also exhibited inflammatory activation. RNA sequencing revealed a significant and sustained activation of type I interferon signaling pathways. Incorporating microglia into sliced neocortical organoids extended the effects of aberrant type I interferon signaling in a human neural context. Collectively, our results illuminate the role of persistent type I interferon signaling in HIV-1 infected microglial in a human neural model, suggesting its potential significance in the pathogenesis of HAND. Highlights of the work HIV-1 productively infects iPSC-derived microglia and triggers inflammatory activation. HIV-1 infection of microglia results in sustained type I interferon signaling. Microglia infected by HIV-1 incorporate into sliced neocortical organoids with persistent type I interferon signaling and disease risk gene expression.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":395273,"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":0.9616,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1170140,"name":"Alessandro C. Stillitano","orcid":"0000-0003-3072-3667","position":1,"is_corresponding":false},{"id":783253,"name":"Hsin-Ching Lin","orcid":null,"position":2,"is_corresponding":false},{"id":1170141,"name":"Yara Abbo","orcid":"0000-0003-3581-7582","position":3,"is_corresponding":false},{"id":79326,"name":"Ronald P. Hart","orcid":"0000-0003-4836-8712","position":4,"is_corresponding":false},{"id":245303,"name":"Peng Jiang","orcid":"0000-0002-2650-3082","position":5,"is_corresponding":false},{"id":330971,"name":"Zhiping P. Pang","orcid":"0000-0002-6183-1233","position":6,"is_corresponding":false},{"id":495407,"name":"Arnold B. Rabson","orcid":"0000-0001-5651-2521","position":7,"is_corresponding":false},{"id":245301,"name":"Andrew J. Boreland","orcid":"0000-0002-1786-3473","position":0,"is_corresponding":true}],"reference_count":123,"raw_metadata":null,"created_at":"2026-07-19T01:19:18.686170Z","pmid":"37961371","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":[]}