{"doi":"10.3390/v17070958","title":"De Novo Expressed Vpr Stimulates HIV-1 Replication in T Cells","abstract":"Vpr, a virion-associated accessory virulence factor of HIV-1, promotes virus replication in both T cells and macrophages. Although Vpr's early activity-antagonism of preintegration silencing and host restriction factors-has been documented, the relative contribution of virion-associated versus de novo expressed Vpr to HIV-1 replication fitness remains unclear. Here, we developed a T cell-based system that genetically separates early and late Vpr functions by combining tetracycline-inducible Vpr expression in CEM.SS T cells with vpr-deficient HIV-1 constructs and Gag p6 mutations that block Vpr packaging. CEM.SS T cells have been shown to recapitulate the positive effect of Vpr on HIV-1 replication observed in activated primary T cells. Using pairwise replication fitness assays under spreading infection conditions, we demonstrate that de novo synthesized Vpr exerts the dominant effect on HIV-1 replication in T cells, while virion-associated Vpr plays a lesser role. Somewhat unexpectedly, our findings reveal that antagonism of preintegration HIV-1 silencing by virion-associated Vpr is unlikely to be the major driver of enhanced HIV-1 replication in proliferating T cells. Instead, this function may play a more prominent role in the infection of non-dividing T cells and/or other cell types.","journal":"Viruses","year":2025,"id":569889,"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":0.9593,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":740828,"name":"Jacek Skowroński","orcid":"0000-0001-7417-0764","position":1,"is_corresponding":false},{"id":1474982,"name":"Blessing Enya","orcid":"0000-0002-5983-1058","position":0,"is_corresponding":true}],"reference_count":69,"raw_metadata":null,"created_at":"2026-07-19T02:57:03.510013Z","pmid":"40733575","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":[]}