{"doi":"10.1371/journal.ppat.1008906","title":"Reactivating latent HIV with PKC agonists induces resistance to apoptosis and is associated with phosphorylation and activation of BCL2","abstract":"Eradication of HIV-1 by the \"kick and kill\" strategy requires reactivation of latent virus to cause death of infected cells by either HIV-induced or immune-mediated apoptosis. To date this strategy has been unsuccessful, possibly due to insufficient cell death in reactivated cells to effectively reduce HIV-1 reservoir size. As a possible cause for this cell death resistance, we examined whether leading latency reversal agents (LRAs) affected apoptosis sensitivity of CD4 T cells. Multiple LRAs of different classes inhibited apoptosis in CD4 T cells. Protein kinase C (PKC) agonists bryostatin-1 and prostratin induced phosphorylation and enhanced neutralizing capability of the anti-apoptotic protein BCL2 in a PKC-dependent manner, leading to resistance to apoptosis induced by both intrinsic and extrinsic death stimuli. Furthermore, HIV-1 producing CD4 T cells expressed more BCL2 than uninfected cells, both in vivo and after ex vivo reactivation. Therefore, activation of BCL2 likely contributes to HIV-1 persistence after latency reversal with PKC agonists. The effects of LRAs on apoptosis sensitivity should be considered in designing HIV cure strategies predicated upon the \"kick and kill\" paradigm.","journal":"PLoS Pathogens","year":2020,"id":93490,"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":40,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9499,"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":468382,"name":"Sekar Natesampillai","orcid":null,"position":1,"is_corresponding":false},{"id":467005,"name":"Ashton Krogman","orcid":"0000-0001-9988-4958","position":2,"is_corresponding":false},{"id":463627,"name":"Cristina Correia","orcid":"0000-0002-9464-7555","position":3,"is_corresponding":false},{"id":468383,"name":"Kevin L. Peterson","orcid":null,"position":4,"is_corresponding":false},{"id":383021,"name":"Alecia Alto","orcid":"0000-0003-2430-4052","position":5,"is_corresponding":false},{"id":467006,"name":"Aswath P. Chandrasekar","orcid":"0000-0002-2352-2456","position":6,"is_corresponding":false},{"id":467007,"name":"Anisha Misra","orcid":"0000-0002-6175-6755","position":7,"is_corresponding":false},{"id":467008,"name":"Ying Li","orcid":"0000-0002-3506-1255","position":8,"is_corresponding":false},{"id":33561,"name":"Scott H. Kaufmann","orcid":"0000-0002-4900-7145","position":9,"is_corresponding":false},{"id":302354,"name":"Andrew D. Badley","orcid":"0000-0001-7796-7680","position":10,"is_corresponding":false},{"id":467009,"name":"Nathan W. Cummins","orcid":"0000-0002-0703-1550","position":11,"is_corresponding":false},{"id":467004,"name":"Andrea French","orcid":"0000-0002-1210-4857","position":0,"is_corresponding":true}],"reference_count":67,"raw_metadata":null,"created_at":"2026-07-18T22:31:34.149524Z","pmid":"33075109","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":[]}