{"doi":"10.3390/pathogens13040292","title":"Complete Rescue of HTLV-1p12KO Infectivity by Depletion of Monocytes Together with NK and CD8+ T Cells","abstract":"The transient depletion of monocytes alone prior to exposure of macaques to HTLV-1 enhances both HTLV-1WT (wild type) and HTLV-1p12KO (Orf-1 knockout) infectivity, but seroconversion to either virus is not sustained over time, suggesting a progressive decrease in virus expression. These results raise the hypotheses that either HTLV-1 persistence depends on a monocyte reservoir or monocyte depletion provides a transient immune evasion benefit. To test these hypotheses, we simultaneously depleted NK cells, CD8+ T cells, and monocytes (triple depletion) prior to exposure to HTLV-1WT or HTLV-1p12KO. Remarkably, triple depletion resulted in exacerbation of infection by both viruses and complete rescue of HTLV-1p12KO infectivity. Following triple depletion, we observed rapid and sustained seroconversion, high titers of antibodies against HTLV-1 p24Gag, and frequent detection of viral DNA in the blood and tissues of all animals when compared with depletion of only CD8+ and NK cells, or monocytes alone. The infection of macaques with HTLV-1WT or HTLV-1p12KO was associated with higher plasma levels of IL-10 after 21 weeks, while IL-6, IFN-γ, IL-18, and IL-1β were only elevated in animals infected with HTLV-1WT. The repeat depletion of monocytes, NK, and CD8+ cells seven months following the first exposure to HTLV-1 did not further exacerbate viral replication. These results underscore the contribution of monocytes in orchestrating anti-viral immunity. Indeed, the absence of orf-1 expression was fully compensated by the simultaneous depletion of CD8+ T cells, NK cells, and monocytes, underlining the primary role of orf-1 in hijacking host immunity.","journal":"Pathogens","year":2024,"id":459366,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9507,"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":409301,"name":"Sarkis Sarkis","orcid":"0000-0002-3876-5733","position":1,"is_corresponding":false},{"id":383714,"name":"Mohammad Arif Rahman","orcid":"0000-0002-6120-8943","position":2,"is_corresponding":false},{"id":240431,"name":"Katherine C. Goldfarbmuren","orcid":"0000-0001-8774-7454","position":3,"is_corresponding":false},{"id":409300,"name":"Ramona Moles","orcid":"0000-0001-8576-2394","position":4,"is_corresponding":false},{"id":397733,"name":"Massimiliano Bissa","orcid":"0000-0003-3455-3992","position":5,"is_corresponding":false},{"id":398793,"name":"Melvin N. Doster","orcid":null,"position":6,"is_corresponding":false},{"id":397735,"name":"Robyn Washington‐Parks","orcid":"0000-0002-5284-9765","position":7,"is_corresponding":false},{"id":893924,"name":"Katherine McKinnon","orcid":"0000-0002-8281-3077","position":8,"is_corresponding":false},{"id":397734,"name":"Isabela Silva de Castro","orcid":"0000-0003-2186-4556","position":9,"is_corresponding":false},{"id":397732,"name":"Luca Schifanella","orcid":"0000-0002-6123-536X","position":10,"is_corresponding":false},{"id":397737,"name":"Genoveffa Franchini","orcid":"0000-0003-2851-6589","position":11,"is_corresponding":false},{"id":893930,"name":"Cynthia A. Pise-Masison","orcid":"0000-0003-2788-235X","position":12,"is_corresponding":false},{"id":893927,"name":"Anna Gutowska","orcid":"0000-0002-9873-6432","position":0,"is_corresponding":true}],"reference_count":102,"raw_metadata":null,"created_at":"2026-07-19T02:03:55.280882Z","pmid":"38668247","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":[]}