{"doi":"10.20411/pai.v9i1.673","title":"Defining the Effects of PKC Modulator HIV Latency-Reversing Agents on Natural Killer Cells","abstract":"Background: Latency reversing agents (LRAs) such as protein kinase C (PKC) modulators can reduce rebound-competent HIV reservoirs in small animal models. Furthermore, administration of natural killer (NK) cells following LRA treatment improves this reservoir reduction. It is currently unknown why the combination of a PKC modulator and NK cells is so potent and whether exposure to PKC modulators may augment NK cell function in some way. Methods: Primary human NK cells were treated with PKC modulators (bryostatin-1, prostratin, or the designed, synthetic bryostatin-1 analog SUW133), and evaluated by examining expression of activation markers by flow cytometry, analyzing transcriptomic profiles by RNA sequencing, measuring cytotoxicity by co-culturing with K562 cells, assessing cytokine production by Luminex assay, and examining the ability of cytokines and secreted factors to independently reverse HIV latency by co-culturing with Jurkat-Latency (J-Lat) cells. Results: PKC modulators increased expression of proteins involved in NK cell activation. Transcriptomic profiles from PKC-treated NK cells displayed signatures of cellular activation and enrichment of genes associated with the NFκB pathway. NK cell cytotoxicity was unaffected by prostratin but significantly decreased by bryostatin-1 and SUW133. Cytokines from PKC-stimulated NK cells did not induce latency reversal in J-Lat cell lines. Conclusions: T cells, not directly enhancing the effector functions of NK cells. This suggests that PKC modulators are primarily augmenting the \"kick\" rather than the \"kill\" arm of this HIV cure approach.","journal":"Pathogens and Immunity","year":2024,"id":478676,"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":2,"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":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":869938,"name":"Jose A. Moran","orcid":"0000-0002-7537-6307","position":1,"is_corresponding":false},{"id":1213946,"name":"Steve Cole","orcid":null,"position":2,"is_corresponding":false},{"id":1011759,"name":"Alok Ranjan","orcid":"0000-0001-9906-4044","position":3,"is_corresponding":false},{"id":1106145,"name":"Rami Hourani","orcid":null,"position":4,"is_corresponding":false},{"id":344319,"name":"Jocelyn T. Kim","orcid":"0000-0001-7040-5773","position":5,"is_corresponding":false},{"id":345109,"name":"Paul A. Wender","orcid":"0000-0001-6319-2829","position":6,"is_corresponding":false},{"id":344317,"name":"Matthew D. Marsden","orcid":"0000-0002-4857-8712","position":7,"is_corresponding":false},{"id":344324,"name":"Jerome A. Zack","orcid":"0000-0001-5486-8495","position":8,"is_corresponding":false},{"id":344321,"name":"Melanie Dimapasoc","orcid":"0000-0003-0328-315X","position":0,"is_corresponding":true}],"reference_count":115,"raw_metadata":null,"created_at":"2026-07-19T02:06:46.330532Z","pmid":"38765786","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":[]}