{"doi":"10.1371/journal.ppat.1008821","title":"Innate, non-cytolytic CD8+ T cell-mediated suppression of HIV replication by MHC-independent inhibition of virus transcription","abstract":"MHC-I-restricted, virus-specific cytotoxic CD8+ T cells (CTLs) may control human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) replication via the recognition and killing of productively infected CD4+ T cells. Several studies in SIV-infected macaques suggest that CD8+ T cells may also decrease virus production by suppressing viral transcription. Here, we show that non-HIV-specific, TCR-activated non-cytolytic CD8+ T cells suppress HIV transcription via a virus- and MHC-independent immunoregulatory mechanism that modulates CD4+ T cell proliferation and activation. We also demonstrate that this CD8+ T cell-mediated effect promotes the survival of infected CD4+ T cells harboring integrated, inducible virus. Finally, we used RNA sequencing and secretome analyses to identify candidate cellular pathways that are involved in the virus-silencing mediated by these CD8+ T cells. This study characterizes a previously undescribed mechanism of immune-mediated HIV silencing that may be involved in the establishment and maintenance of the reservoir under antiretroviral therapy and therefore represent a major obstacle to HIV eradication.","journal":"PLoS Pathogens","year":2020,"id":93456,"datarank":0.5570358100056463,"base_score":3.713572066704308,"endowment":3.713572066704308,"self_citation_contribution":0.5570358100056463,"citation_network_contribution":0.0,"self_endowment_contribution":0.5570358100056463,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":40,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.949,"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":468351,"name":"David Palesch","orcid":null,"position":1,"is_corresponding":false},{"id":466904,"name":"Claudia Pinacchio","orcid":"0000-0003-4370-3366","position":2,"is_corresponding":false},{"id":466905,"name":"Maura Statzu","orcid":"0000-0003-0070-2195","position":3,"is_corresponding":false},{"id":244967,"name":"Gregory K. Tharp","orcid":"0000-0003-3075-755X","position":4,"is_corresponding":false},{"id":244985,"name":"Mirko Paiardini","orcid":"0000-0002-7276-3600","position":5,"is_corresponding":false},{"id":94485,"name":"Ann Chahroudi","orcid":"0000-0001-7479-9546","position":6,"is_corresponding":false},{"id":232942,"name":"Steven E. Bosinger","orcid":"0000-0002-2116-5061","position":7,"is_corresponding":false},{"id":468352,"name":"Jack Yoon","orcid":null,"position":8,"is_corresponding":false},{"id":375882,"name":"Bryan D. Cox","orcid":"0000-0002-6851-9007","position":9,"is_corresponding":false},{"id":233497,"name":"Guido Silvestri","orcid":"0000-0001-6602-2470","position":10,"is_corresponding":false},{"id":247225,"name":"Deanna A. Kulpa","orcid":"0000-0002-0411-7295","position":11,"is_corresponding":false},{"id":466903,"name":"Michelle Zanoni","orcid":"0000-0002-7975-9997","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T22:31:34.149524Z","pmid":"32941545","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":[]}