{"doi":"10.1371/journal.ppat.1011844","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":"PLoS Pathogens","year":2023,"id":353392,"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":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9459,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":372011,"name":"Anil Verma","orcid":"0000-0002-0024-7826","position":1,"is_corresponding":false},{"id":557443,"name":"Zhong-Min Ma","orcid":"0000-0003-3713-7337","position":2,"is_corresponding":false},{"id":636979,"name":"Sean Ott","orcid":"0000-0001-8792-7236","position":3,"is_corresponding":false},{"id":320291,"name":"Dhivyaa Rajasundaram","orcid":"0000-0001-7417-8002","position":4,"is_corresponding":false},{"id":459156,"name":"Chase E. Hawes","orcid":"0000-0002-5927-9793","position":5,"is_corresponding":false},{"id":558226,"name":"Yashavanth Shaan Lakshmanappa","orcid":null,"position":6,"is_corresponding":false},{"id":370688,"name":"Mackenzie L. Cottrell","orcid":"0000-0002-0291-5111","position":7,"is_corresponding":false},{"id":370695,"name":"Angela D. M. Kashuba","orcid":"0000-0002-9171-8493","position":8,"is_corresponding":false},{"id":307291,"name":"Zandrea Ambrose","orcid":"0000-0002-8610-2766","position":9,"is_corresponding":false},{"id":233484,"name":"Jeffrey D. Lifson","orcid":"0000-0002-9494-0268","position":10,"is_corresponding":false},{"id":515987,"name":"John H. Morrison","orcid":"0000-0002-8292-0964","position":11,"is_corresponding":false},{"id":297247,"name":"Smita S. Iyer","orcid":"0000-0002-8918-7005","position":12,"is_corresponding":false},{"id":557438,"name":"Sonny R. Elizaldi","orcid":"0000-0001-7464-8721","position":0,"is_corresponding":true}],"reference_count":73,"raw_metadata":null,"created_at":"2026-07-19T01:12:58.542950Z","pmid":"38060615","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":[]}