{"doi":"10.1101/2021.01.25.428084","title":"HIV-1 Vpr drives a tissue residency-like phenotype during selective infection of resting memory T cells","abstract":"Human immunodeficiency virus type 1 (HIV-1) replicates in CD4+ T cells leading to profound T cell loss, immunological dysfunction and AIDS. Determining how HIV-1 shapes the immunological niche in which it resides to create a permissive environment is central to informing efforts to limit pathogenesis, disturb viral reservoirs and achieve a cure. A key roadblock in understanding HIV-T cell interactions is the requirement to activate CD4+ T cells in vitro in order to make them permissive to infection. This dramatically alters T cell biology, obscuring native virus-host interactions. Here we show that HIV-1 cell-to-cell spread permits efficient and productive infection of resting CD4+ T cells without the need for prior activation. Infection is preferential for resting memory T cells, is observed with both CXCR4-tropic virus and CCR5-tropic transmitter-founder viruses and results in virus production and onward spreading infection. Strikingly, we find that HIV-1 infection of resting memory CD4+ T cells primes for induction of a tissue-resident memory (T RM )-like phenotype evidenced by upregulation of T RM markers CD69/CXCR6 alongside co-expression of CD49a, PD-1, CD101 as well as transcription factor Blimp-1. Furthermore, we reveal that HIV-1 initiates a transcriptional program that overlaps with the core T RM transcriptional signature. This reprograming depends on the HIV-1 accessory protein Vpr. We propose that HIV-1 infection drives a CD4+ T RM -phenotype potentially sequestering infected cells within tissues to support viral replication and persistence.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":220144,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9533,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":819296,"name":"Maitreyi Shivkumar","orcid":"0000-0002-1559-5583","position":1,"is_corresponding":false},{"id":2376,"name":"Dejan Mesner","orcid":"0000-0002-7109-4011","position":2,"is_corresponding":false},{"id":283776,"name":"Laura J. Pallett","orcid":null,"position":3,"is_corresponding":false},{"id":819297,"name":"José Afonso Guerra‐Assunção","orcid":"0000-0001-6593-403X","position":4,"is_corresponding":false},{"id":570699,"name":"Rajhmun Madansein","orcid":"0000-0001-7306-1304","position":5,"is_corresponding":false},{"id":819298,"name":"Kaylesh J Dullabh","orcid":"0000-0002-2469-871X","position":6,"is_corresponding":false},{"id":584140,"name":"Alex Sigal","orcid":"0000-0001-8571-2004","position":7,"is_corresponding":false},{"id":819299,"name":"John Thornhill","orcid":"0000-0002-2174-9446","position":8,"is_corresponding":false},{"id":378906,"name":"Carolina Herrera","orcid":"0000-0003-3701-752X","position":9,"is_corresponding":false},{"id":257500,"name":"Sarah Fidler","orcid":"0000-0003-1676-7583","position":10,"is_corresponding":false},{"id":1487,"name":"Mahdad Noursadeghi","orcid":"0000-0002-4774-0853","position":11,"is_corresponding":false},{"id":240227,"name":"Mala K. Maini","orcid":"0000-0001-6384-1462","position":12,"is_corresponding":false},{"id":1490,"name":"Clare Jolly","orcid":"0000-0002-4603-2281","position":13,"is_corresponding":false},{"id":1492,"name":"Ann‐Kathrin Reuschl","orcid":"0000-0002-1459-3519","position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-07-18T23:53:42.928212Z","pmid":null,"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":[]}