{"doi":"10.17615/r5qp-d365","title":"Spatiotemporal trafficking of HIV in human plasmacytoid dendritic cells defines a persistently IFN-α–producing and partially matured phenotype","abstract":"Plasmacytoid DCs (pDCs) are innate immune cells that are specialized to produce IFN-α and to activate adaptive immune responses. Although IFN-α inhibits HIV-1 replication in vitro, the production of IFN-α by HIV-activated pDCs in vivo may contribute more to HIV pathogenesis than to protection. We have now shown that HIV-stimulated human pDCs allow for persistent IFN-α production upon repeated stimulation, express low levels of maturation molecules, and stimulate weak T cell responses. Persistent IFN-α production by HIV-stimulated pDCs correlated with increased levels of IRF7 and was dependent upon the autocrine IFN-α/β receptor feedback loop. Because it has been shown that early endosomal trafficking of TLR9 agonists causes strong activation of the IFN-α pathway but weak activation of the NF-κB pathway, we sought to investigate whether early endosomal trafficking of HIV, a TLR7 agonist, leads to the IFN-α–producing phenotype we observed. We demonstrated that HIV preferentially traffics to the early endosome in human pDCs and therefore skews pDCs toward a partially matured, persistently IFN-α–secreting phenotype.","journal":"UNC Libraries","year":2020,"id":136994,"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":0.9495,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":596857,"name":"Linda Rolnitzky","orcid":null,"position":1,"is_corresponding":false},{"id":86525,"name":"Nina Bhardwaj","orcid":"0000-0003-1865-4187","position":2,"is_corresponding":false},{"id":596858,"name":"Meagan P. O’Brien","orcid":null,"position":3,"is_corresponding":false},{"id":596193,"name":"Yaming Wang","orcid":"0000-0002-8208-8696","position":4,"is_corresponding":false},{"id":596859,"name":"Rachel Lubong Sabado","orcid":null,"position":5,"is_corresponding":false},{"id":105520,"name":"David M. Margolis","orcid":"0000-0001-5714-0002","position":6,"is_corresponding":false},{"id":596860,"name":"Sonia Jimenez Baranda","orcid":null,"position":7,"is_corresponding":false},{"id":596861,"name":"I. Marie","orcid":null,"position":8,"is_corresponding":false},{"id":524564,"name":"Martin Markowitz","orcid":null,"position":9,"is_corresponding":false},{"id":596194,"name":"Olivier Manches","orcid":"0000-0003-4509-2941","position":10,"is_corresponding":false},{"id":136281,"name":"David Levy","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:16:52.487376Z","pmid":null,"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":[]}