{"doi":"10.17615/s3c2-sv74","title":"Deep analysis of CD4 T cells in the rhesus CNS during SIV infection","abstract":"Virologic suppression with antiretroviral therapy (ART) has significantly improved health outcomes for people living with HIV, yet challenges related to chronic inflammation in the central nervous system (CNS)—known as Neuro-HIV- persist. As primary targets for HIV-1 with the ability to survey and populate the CNS and interact with myeloid cells to co-ordinate neuroinflammation, CD4 T cells are pivotal in Neuro-HIV. Despite their importance, our understanding of CD4 T cell distribution in virus-targeted CNS tissues, their response to infection, and potential recovery following initiation of ART remain limited. To address these gaps, we studied ten SIVmac251-infected rhesus macaques using an ART regimen simulating suboptimal adherence. We evaluated four macaques during the acute phase pre-ART and six during the chronic phase. Our data revealed that HIV target CCR5+ CD4 T cells inhabit both the brain parenchyma and adjacent CNS tissues, encompassing choroid plexus stroma, dura mater, and the skull bone marrow. Aligning with the known susceptibility of CCR5+ CD4 T cells to viral infection and their presence within the CNS, high levels of viral RNA were detected in the brain parenchyma and its border tissues during acute SIV infection. Single-cell RNA sequencing of CD45+ cells from the brain revealed colocalization of viral transcripts within CD4 clusters and significant activation of antiviral molecules and specific effector programs within T cells, indicating CNS CD4 T cell engagement during infection. Acute infection led to marked imbalance in the CNS CD4/CD8 ratio which persisted into the chronic phase. These observations underscore the functional involvement of CD4 T cells within the CNS during SIV infection, enhancing our understanding of their role in establishing CNS viral presence. Our findings offer insights for potential T cell-focused interventions while underscoring the challenges in eradicating HIV from the CNS, particularly in the context of sub-optimal ART.","journal":"UNC Libraries","year":2024,"id":498819,"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":0.9446,"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":1345859,"name":"Ott S.","orcid":null,"position":1,"is_corresponding":false},{"id":1345860,"name":"Kashuba A.D.M.","orcid":null,"position":2,"is_corresponding":false},{"id":1345861,"name":"Hawes C.E.","orcid":null,"position":3,"is_corresponding":false},{"id":1345862,"name":"Iyer S.S.","orcid":null,"position":4,"is_corresponding":false},{"id":1345863,"name":"Ma Z.-M.","orcid":null,"position":5,"is_corresponding":false},{"id":1345864,"name":"Elizaldi S.R.","orcid":null,"position":6,"is_corresponding":false},{"id":1345865,"name":"Lakshmanappa Y.S.","orcid":null,"position":7,"is_corresponding":false},{"id":320291,"name":"Dhivyaa Rajasundaram","orcid":"0000-0001-7417-8002","position":8,"is_corresponding":false},{"id":1345866,"name":"Cottrell M.L.","orcid":null,"position":9,"is_corresponding":false},{"id":307291,"name":"Zandrea Ambrose","orcid":"0000-0002-8610-2766","position":10,"is_corresponding":false},{"id":372011,"name":"Anil Verma","orcid":"0000-0002-0024-7826","position":11,"is_corresponding":false},{"id":1345867,"name":"Morrison J.H.","orcid":null,"position":12,"is_corresponding":false},{"id":1345858,"name":"Lifson J.D.","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:09:42.181447Z","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":[]}