{"doi":"10.3390/v17040467","title":"Microglia Exhibit a Unique Intact HIV Reservoir in Human Postmortem Brain Tissue","abstract":"<jats:p>A proviral reservoir persists within the central nervous system (CNS) of people with HIV, but its characteristics remain poorly understood. Research has primarily focused on cerebrospinal fluid (CSF), as acquiring brain tissue is challenging. We examined size, cellular tropism, and infection-dynamics of the viral reservoir in post-mortem brain tissue from five individuals on and off antiretroviral therapy (ART) across three brain regions. Microglia-enriched fractions (CD11b+) were isolated and levels of intact proviral DNA were quantified (IPDA). Full-length envelope reporter viruses were generated and characterized in CD4+ T cells and monocyte-derived microglia. HIV DNA was observed in microglia-enriched fractions of all individuals, but intact proviruses were identified only in one ART-treated individual, representing 15% of the total proviruses. Phenotypic analyses of clones from this individual showed that 80% replicated efficiently in microglia and CD4+ T cells, while the remaining viruses replicated only in CD4+ T cells. No region-specific effects were observed. These results indicate a distinct HIV brain reservoir in microglia for all individuals, although intact proviruses were detected in only one. Given the unique immune environment of the CNS, the characteristics of microglia, and the challenges associated with targeting these cells, the CNS reservoir should be considered in cure strategies.</jats:p>","journal":"Viruses","year":2025,"id":608379,"datarank":0.40620753016533157,"base_score":2.70805020110221,"endowment":2.70805020110221,"self_citation_contribution":0.40620753016533157,"citation_network_contribution":0.0,"self_endowment_contribution":0.40620753016533157,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":511482,"name":"Stephanie B. 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We examined size, cellular tropism, and infection-dynamics of the viral reservoir in post-mortem brain tissue from five individuals on and off antiretroviral therapy (ART) across three brain regions. Microglia-enriched fractions (CD11b+) were isolated and levels of intact proviral DNA were quantified (IPDA). Full-length envelope reporter viruses were generated and characterized in CD4+ T cells and monocyte-derived microglia. HIV DNA was observed in microglia-enriched fractions of all individuals, but intact proviruses were identified only in one ART-treated individual, representing 15% of the total proviruses. Phenotypic analyses of clones from this individual showed that 80% replicated efficiently in microglia and CD4+ T cells, while the remaining viruses replicated only in CD4+ T cells. No region-specific effects were observed. These results indicate a distinct HIV brain reservoir in microglia for all individuals, although intact proviruses were detected in only one. Given the unique immune environment of the CNS, the characteristics of microglia, and the challenges associated with targeting these cells, the CNS reservoir should be considered in cure strategies.</jats:p>","is_dataset_classified":null,"base_score":2.4849066497880004,"endowment":2.4849066497880004,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"40284910","pmcid":null,"openalex_id":"https://openalex.org/W4408808583","authors":[],"funders":[{"funder_name":"Aidsfonds","grant_id":"P-13204","title":null},{"funder_name":"Aidsfonds","grant_id":"P-66401","title":null},{"funder_name":"Aidsfonds","grant_id":"LSHM2OO12-SGF","title":null},{"funder_name":"Aidsfonds","grant_id":"LSHM19100-SGF","title":null},{"funder_name":"Aidsfonds","grant_id":"LSHM19101-SGF","title":null},{"funder_name":"Aidsfonds","grant_id":"U24MH100931","title":null},{"funder_name":"Aidsfonds","grant_id":"75N95023C00015","title":null},{"funder_name":"National Institutes of Health","grant_id":"3U24MH100931-08S1","title":"The Manhattan HIV Brain Bank"}],"total_grants":8,"fwci":6.9619,"citation_percentile":0.9749014,"influential_citations":0,"citation_trend":[{"year":2025,"count":2},{"year":2026,"count":9}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.mdpi.com/1999-4915/17/4/467/pdf?version=1742895826","host_type":"journal"},{"url":"https://www.mdpi.com/1999-4915/17/4/467/pdf?version=1742895826","host_type":"publisher"},{"url":"https://www.mdpi.com/1999-4915/17/4/467/pdf","host_type":"publisher"},{"url":"https://doi.org/10.3390/v17040467","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40284910","host_type":"repository"},{"url":"https://hdl.handle.net/2066/319120","host_type":"repository"},{"url":"https://doaj.org/article/c3387b545b2e4ced8fe474a5a92143f1","host_type":"repository"},{"url":"https://dspace.library.uu.nl/handle/1874/465914","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/12030925","host_type":"repository"},{"url":"https://repository.ubn.ru.nl//bitstream/handle/2066/319120/319120.pdf","host_type":"repository"},{"url":"http://dx.doi.org/10.3390/v17040467","host_type":""},{"url":"https://hdl.handle.net/https://repository.ubn.ru.nl/handle/2066/319120","host_type":""},{"url":"https://dx.doi.org/10.3390/v17040467","host_type":""}],"fields_of_study":["HIV Research and Treatment","Neuroinflammation and Neurodegeneration Mechanisms","Cytomegalovirus and herpesvirus research","0301 basic medicine","03 medical and health sciences"],"mesh_terms":["Adult","Autopsy","Brain","Disease Reservoirs","DNA, Viral","Female","Humans","Male","Middle Aged","Proviruses","Virus Replication","CD4-Positive T-Lymphocytes","HIV-1","HIV Infections","Microglia","Viral Load"],"keywords":["Microglia","Biology","Immune system","Central nervous system","Tissue tropism","Virology","Cerebrospinal fluid","Phenotype","Tropism","Brain tissue","Immunology","Virus","Neuroscience","Gene","Inflammation","Genetics","CD4-Positive T-Lymphocytes","Male","Adult","brain","HIV Infections","Virus Replication","Microbiology","Article","Proviruses","Humans","Disease Reservoirs","replication-competent","cellular tropism","HIV","Middle Aged","Viral Load","QR1-502","DNA, Viral","Psychiatry - Development and lifelong plasticity","HIV-1","Human Genetics - Development and lifelong plasticity","Female","Autopsy","CNS"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-30T12:40:47.882636Z","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":[]}