{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T01:30:59Z","timestamp":1791595859928,"version":"4.3.4"},"reference-count":62,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T00:00:00Z","timestamp":1742860800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Aidsfonds","award":["P-13204"],"award-info":[{"award-number":["P-13204"]}]},{"name":"Aidsfonds","award":["P-66401"],"award-info":[{"award-number":["P-66401"]}]},{"name":"Aidsfonds","award":["LSHM2OO12-SGF"],"award-info":[{"award-number":["LSHM2OO12-SGF"]}]},{"name":"Aidsfonds","award":["LSHM19100-SGF"],"award-info":[{"award-number":["LSHM19100-SGF"]}]},{"name":"Aidsfonds","award":["LSHM19101-SGF"],"award-info":[{"award-number":["LSHM19101-SGF"]}]},{"name":"Aidsfonds","award":["U24MH100931"],"award-info":[{"award-number":["U24MH100931"]}]},{"name":"Aidsfonds","award":["75N95023C00015"],"award-info":[{"award-number":["75N95023C00015"]}]},{"name":"Health Holland","award":["P-13204"],"award-info":[{"award-number":["P-13204"]}]},{"name":"Health Holland","award":["P-66401"],"award-info":[{"award-number":["P-66401"]}]},{"name":"Health Holland","award":["LSHM2OO12-SGF"],"award-info":[{"award-number":["LSHM2OO12-SGF"]}]},{"name":"Health Holland","award":["LSHM19100-SGF"],"award-info":[{"award-number":["LSHM19100-SGF"]}]},{"name":"Health Holland","award":["LSHM19101-SGF"],"award-info":[{"award-number":["LSHM19101-SGF"]}]},{"name":"Health Holland","award":["U24MH100931"],"award-info":[{"award-number":["U24MH100931"]}]},{"name":"Health Holland","award":["75N95023C00015"],"award-info":[{"award-number":["75N95023C00015"]}]},{"name":"KNAW Van Leursum beurs","award":["P-13204"],"award-info":[{"award-number":["P-13204"]}]},{"name":"KNAW Van Leursum beurs","award":["P-66401"],"award-info":[{"award-number":["P-66401"]}]},{"name":"KNAW Van Leursum beurs","award":["LSHM2OO12-SGF"],"award-info":[{"award-number":["LSHM2OO12-SGF"]}]},{"name":"KNAW Van Leursum beurs","award":["LSHM19100-SGF"],"award-info":[{"award-number":["LSHM19100-SGF"]}]},{"name":"KNAW Van Leursum beurs","award":["LSHM19101-SGF"],"award-info":[{"award-number":["LSHM19101-SGF"]}]},{"name":"KNAW Van Leursum beurs","award":["U24MH100931"],"award-info":[{"award-number":["U24MH100931"]}]},{"name":"KNAW Van Leursum beurs","award":["75N95023C00015"],"award-info":[{"award-number":["75N95023C00015"]}]},{"name":"Manhattan HIV Brain Bank","award":["P-13204"],"award-info":[{"award-number":["P-13204"]}]},{"name":"Manhattan HIV Brain Bank","award":["P-66401"],"award-info":[{"award-number":["P-66401"]}]},{"name":"Manhattan HIV Brain Bank","award":["LSHM2OO12-SGF"],"award-info":[{"award-number":["LSHM2OO12-SGF"]}]},{"name":"Manhattan HIV Brain Bank","award":["LSHM19100-SGF"],"award-info":[{"award-number":["LSHM19100-SGF"]}]},{"name":"Manhattan HIV Brain Bank","award":["LSHM19101-SGF"],"award-info":[{"award-number":["LSHM19101-SGF"]}]},{"name":"Manhattan HIV Brain Bank","award":["U24MH100931"],"award-info":[{"award-number":["U24MH100931"]}]},{"name":"Manhattan HIV Brain Bank","award":["75N95023C00015"],"award-info":[{"award-number":["75N95023C00015"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"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>","DOI":"10.3390\/v17040467","type":"journal-article","created":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T06:25:15Z","timestamp":1742883915000},"page":"467","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Microglia Exhibit a Unique Intact HIV Reservoir in Human Postmortem Brain Tissue"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4360-0431","authenticated-orcid":false,"given":"Marieke M.","family":"N\u00fchn","sequence":"first","affiliation":[{"name":"Translational Virology, Department of Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie B. H.","family":"Gumbs","sequence":"additional","affiliation":[{"name":"Translational Virology, Department of Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pauline J.","family":"Schipper","sequence":"additional","affiliation":[{"name":"Translational Virology, Department of Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2740-2213","authenticated-orcid":false,"given":"Irene","family":"Drosou","sequence":"additional","affiliation":[{"name":"Translational Virology, Department of Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lavina","family":"Gharu","sequence":"additional","affiliation":[{"name":"Translational Virology, Department of Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4545-7536","authenticated-orcid":false,"given":"Nin\u00e9e V. E. J.","family":"Buchholtz","sequence":"additional","affiliation":[{"name":"Translational Virology, Department of Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gijsje J. L. J.","family":"Snijders","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederieke A. J.","family":"Gigase","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemarie M. J.","family":"Wensing","sequence":"additional","affiliation":[{"name":"Translational Virology, Department of Global Health and Bioethics, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jori","family":"Symons","sequence":"additional","affiliation":[{"name":"Translational Virology, Department of Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lot D.","family":"de Witte","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"},{"name":"Department of Psychiatry, Radboud UMC, 6525 GA Nijmegen, The Netherlands"},{"name":"Department of Human Genetics, Radboud UMC, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6610-8282","authenticated-orcid":false,"given":"Monique","family":"Nijhuis","sequence":"additional","affiliation":[{"name":"Translational Virology, Department of Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"13193","DOI":"10.1073\/pnas.94.24.13193","article-title":"Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy","volume":"94","author":"Chun","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"10958","DOI":"10.1073\/pnas.96.20.10958","article-title":"Latent reservoir of HIV: Obstacles to the eradication of the virus","volume":"96","author":"Chun","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1126\/science.278.5341.1295","article-title":"Identification of a Reservoir for HIV-1 in Patients on Highly Active Antiretroviral Therapy","volume":"278","author":"Finzi","year":"1997","journal-title":"Science"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1002\/JLB.2RI0517-200R","article-title":"The evolution of HIV-1 entry phenotypes as a guide to changing target cells","volume":"103","author":"Joseph","year":"2018","journal-title":"J. Leukoc. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1097\/COH.0000000000000293","article-title":"Tissue reservoirs of HIV","volume":"11","author":"Wong","year":"2016","journal-title":"Curr. Opin. HIV AIDS"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"11294","DOI":"10.1128\/JVI.00946-15","article-title":"Phenotypic Correlates of HIV-1 Macrophage Tropism","volume":"89","author":"Arrildt","year":"2015","journal-title":"J. Virol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1002\/JLB.5VMR0122-046RRR","article-title":"Shock and kill within the CNS: A promising HIV eradication approach?","volume":"112","author":"Gumbs","year":"2022","journal-title":"J. Leukoc. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1080\/13550280600748946","article-title":"Use of laser capture microdissection to detect integrated HIV-1 DNA in macrophages and astrocytes from autopsy brain tissues","volume":"12","author":"Churchill","year":"2006","journal-title":"J. Neurovirol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1016\/j.ajpath.2011.06.039","article-title":"Brain Cell Reservoirs of Latent Virus in Presymptomatic HIV-Infected Individuals","volume":"179","author":"Thompson","year":"2011","journal-title":"Am. J. Pathol."},{"key":"ref_10","first-page":"144","article-title":"Detection of HIV-1 DNA in Microglia\/ Macrophages, Astrocytes and Neurons Isolated from Brain Tissue with HIV-1 Encephalitis by Laser Capture Microdissection","volume":"13","author":"Diamanturos","year":"2006","journal-title":"Brain Pathol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1002\/ana.26456","article-title":"Intact HIV Proviruses Persist in the Brain Despite Viral Suppression with ART","volume":"92","author":"Cochrane","year":"2022","journal-title":"Ann. Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1007\/s11481-018-9809-2","article-title":"Macrophages but not Astrocytes Harbor HIV DNA in the Brains of HIV-1-Infected Aviremic Individuals on Suppressive Antiretroviral Therapy","volume":"14","author":"Ko","year":"2018","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Jamal Eddine, J., Angelovich, T.A., Zhou, J., Byrnes, S.J., Tumpach, C., Saraya, N., Chalmers, E., Shepherd, R.A., Tan, A., and Marinis, S. (2024). HIV transcription persists in the brain of virally suppressed people with HIV. PLoS Pathog., 20.","DOI":"10.1371\/journal.ppat.1012446"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Wallet, C., De Rovere, M., Van Assche, J., Daouad, F., De Wit, S., Gautier, V., Mallon, P.W.G., Marcello, A., Van Lint, C., and Rohr, O. (2019). Microglial Cells: The Main HIV-1 Reservoir in the Brain. Front. Cell Infect. Microbiol., 9.","DOI":"10.3389\/fcimb.2019.00362"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e167417","DOI":"10.1172\/JCI167417","article-title":"Brain microglia serve as a persistent HIV reservoir despite durable antiretroviral therapy","volume":"133","author":"Tang","year":"2023","journal-title":"J. Clin. Investig."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"RP89837","DOI":"10.7554\/eLife.89837.3","article-title":"Persistence of intact HIV-1 proviruses in the brain during antiretroviral therapy","volume":"12","author":"Sun","year":"2023","journal-title":"eLife"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1002\/ana.26750","article-title":"Regional Analysis of Intact and Defective HIV Proviruses in the Brain of Viremic and Virally Suppressed People with HIV","volume":"94","author":"Angelovich","year":"2023","journal-title":"Ann. Neurol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Gabuzda, D., Yin, J., Misra, V., Chettimada, S., and Gelman, B.B. (2023). Intact Proviral DNA Analysis of the Brain Viral Reservoir and Relationship to Neuroinflammation in People with HIV on Suppressive Antiretroviral Therapy. Viruses, 15.","DOI":"10.3390\/v15041009"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1038\/ni.3666","article-title":"The movers and shapers in immune privilege of the CNS","volume":"18","author":"Engelhardt","year":"2017","journal-title":"Nat. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1007\/s00281-022-00926-8","article-title":"T-cell surveillance of the human brain in health and multiple sclerosis","volume":"44","author":"Smolders","year":"2022","journal-title":"Semin. Immunopathol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Sturdevant, C.B., Joseph, S.B., Schnell, G., Price, R.W., Swanstrom, R., and Spudich, S. (2015). Compartmentalized Replication of R5 T Cell-Tropic HIV-1 in the Central Nervous System Early in the Course of Infection. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1004720"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Schnell, G., Joseph, S., Spudich, S., Price, R.W., and Swanstrom, R. (2011). HIV-1 Replication in the Central Nervous System Occurs in Two Distinct Cell Types. PLoS Pathog., 7.","DOI":"10.1371\/journal.ppat.1002286"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1007\/s13365-024-01207-w","article-title":"Characterization of HIV variants from paired Cerebrospinal fluid and Plasma samples in primary microglia and CD4(+) T-cells","volume":"30","author":"Gumbs","year":"2024","journal-title":"J. Neurovirol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1093\/cid\/ciy1066","article-title":"Human Immunodeficiency Virus Type 1 RNA Detected in the Central Nervous System (CNS) After Years of Suppressive Antiretroviral Therapy Can Originate from a Replicating CNS Reservoir or Clonally Expanded Cells","volume":"69","author":"Joseph","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_25","first-page":"260","article-title":"Rebound HIV-1 in cerebrospinal fluid after antiviral therapy interruption is mainly clonally amplified R5 T cell-tropic virus","volume":"8","author":"Kincer","year":"2023","journal-title":"Nat. Microbiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1038\/s41586-019-0898-8","article-title":"A quantitative approach for measuring the reservoir of latent HIV-1 proviruses","volume":"566","author":"Bruner","year":"2019","journal-title":"Nature"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s12985-024-02300-6","article-title":"Development of a highly sensitive and specific intact proviral DNA assay for HIV-1 subtype B and C","volume":"21","author":"Buchholtz","year":"2024","journal-title":"Virol. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1007\/s13365-021-01049-w","article-title":"Human microglial models to study HIV infection and neuropathogenesis: A literature overview and comparative analyses","volume":"28","author":"Gumbs","year":"2022","journal-title":"J. Neurovirol"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.bbi.2020.08.012","article-title":"A characterization of the molecular phenotype and inflammatory response of schizophrenia patient-derived microglia-like cells","volume":"90","author":"Ormel","year":"2020","journal-title":"Brain Behav. Immun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1038\/s41398-019-0490-x","article-title":"Microglia in post-mortem brain tissue of patients with bipolar disorder are not immune activated","volume":"9","author":"Sneeboer","year":"2019","journal-title":"Transl. Psychiatry"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e25185","DOI":"10.1002\/jia2.25185","article-title":"Development of sensitive ddPCR assays to reliably quantify the proviral DNA reservoir in all common circulating HIV subtypes and recombinant forms","volume":"21","author":"Bosman","year":"2018","journal-title":"J. Int. AIDS Soc."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"N\u00fchn, M.M., Bosman, K., Huisman, T., Staring, W.H.A., Gharu, L., De Jong, D., De Kort, T.M., Buchholtz, N., Tesselaar, K., and Pandit, A. (2025). Selective decline of intact HIV reservoirs during the first decade of ART followed by stabilization in memory T cell subsets. AIDS, online ahead of print.","DOI":"10.1097\/QAD.0000000000004160"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Buchholtz, N.V.E.J., Hermans, L.E., Umunnakwe, C.N., N\u00fchn, M.M., Voss, R., Need, E., Kootstra, N.A., Maurer, I., de Jong, D.C.M., and Symons, J. (2024). Defective proviruses significantly impact viral transcription and immune activation in men and women with HIV-1 subtype C in rural South Africa. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1484358"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1038\/nbt1371","article-title":"Bioinformatics prediction of HIV coreceptor usage","volume":"25","author":"Lengauer","year":"2007","journal-title":"Nat. Biotechnol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1002\/glia.22370","article-title":"Phenotyping primary human microglia: Tight regulation of LPS responsiveness","volume":"60","author":"Melief","year":"2012","journal-title":"Glia"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1848","DOI":"10.1002\/glia.22562","article-title":"Microglia in normal appearing white matter of multiple sclerosis are alerted but immunosuppressed","volume":"61","author":"Melief","year":"2013","journal-title":"Glia"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1857","DOI":"10.1002\/glia.23023","article-title":"Characterizing primary human microglia: A comparative study with myeloid subsets and culture models","volume":"64","author":"Melief","year":"2016","journal-title":"Glia"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"100035","DOI":"10.1016\/j.xpro.2020.100035","article-title":"Isolation of Microglia from Mouse or Human Tissue","volume":"1","author":"Bordt","year":"2020","journal-title":"STAR Protoc."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Mattei, D., Ivanov, A., van Oostrum, M., Pantelyushin, S., Richetto, J., Mueller, F., Beffinger, M., Schellhammer, L., Vom Berg, J., and Wollscheid, B. (2020). Enzymatic Dissociation Induces Transcriptional and Proteotype Bias in Brain Cell Populations. Int. J. Mol. Sci., 21.","DOI":"10.1101\/2020.05.14.095422"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1007\/s11904-015-0265-9","article-title":"Compartmentalization, Viral Evolution, and Viral Latency of HIV in the CNS","volume":"12","author":"Bednar","year":"2015","journal-title":"Curr. HIV\/AIDS Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1097\/COH.0000000000000108","article-title":"Is the central nervous system a reservoir of HIV-1?","volume":"9","author":"Gray","year":"2014","journal-title":"Curr. Opin. HIV AIDS"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1007\/s13365-018-0633-5","article-title":"Ultradeep single-molecule real-time sequencing of HIV envelope reveals complete compartmentalization of highly macrophage-tropic R5 proviral variants in brain and CXCR4-using variants in immune and peripheral tissues","volume":"24","author":"Brese","year":"2018","journal-title":"J. Neurovirol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s12974-024-03015-9","article-title":"Taming microglia: The promise of engineered microglia in treating neurological diseases","volume":"21","author":"Luo","year":"2024","journal-title":"J. Neuroinflamm."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e202402736","DOI":"10.26508\/lsa.202402736","article-title":"Gene expression and chromatin conformation of microglia in virally suppressed people with HIV","volume":"7","author":"Schlachetzki","year":"2024","journal-title":"Life Sci. Alliance"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e132997","DOI":"10.1172\/jci.insight.132997","article-title":"Differential decay of intact and defective proviral DNA in HIV-1-infected individuals on suppressive antiretroviral therapy","volume":"5","author":"Peluso","year":"2020","journal-title":"JCI Insight"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e2120326119","DOI":"10.1073\/pnas.2120326119","article-title":"Complex decay dynamics of HIV virions, intact and defective proviruses, and 2LTR circles following initiation of antiretroviral therapy","volume":"119","author":"White","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_47","unstructured":"Basson, A., Sabet, N., Omar, T., Moodie, M., Nijhuis, M., Wensing, A.M.J., Tiemessen, C.T., Venter, F., Variava, E., and Martinson, N. (2024). Minimally Invasive Autopsy Confirms HIV-1 Persistence in Multiple Compartments Despite Prolonged cART, in Poster, CROI 2024."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1111\/j.1600-065X.2006.00441.x","article-title":"CNS immune privilege: Hiding in plain sight","volume":"213","author":"Carson","year":"2006","journal-title":"Immunol. Rev."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1038\/s41590-018-0085-3","article-title":"Resistance of HIV-infected macrophages to CD8 (+) T lymphocyte-mediated killing drives activation of the immune system","volume":"19","author":"Clayton","year":"2018","journal-title":"Nat. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1038\/s41380-019-0609-8","article-title":"Microglial regional heterogeneity and its role in the brain","volume":"25","author":"Tan","year":"2020","journal-title":"Mol. Psychiatry"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/s41588-021-00976-y","article-title":"Genetic analysis of the human microglial transcriptome across brain regions, aging and disease pathologies","volume":"54","author":"Lopes","year":"2022","journal-title":"Nat. Genet."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e0054323","DOI":"10.1128\/jvi.00543-23","article-title":"Evaluation of Archival HIV DNA in Brain and Lymphoid Tissues","volume":"97","author":"Oliveira","year":"2023","journal-title":"J. Virol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1172\/JCI134815","article-title":"HIV persists throughout deep tissues with repopulation from multiple anatomical sources","volume":"130","author":"Chaillon","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"8984","DOI":"10.1128\/JVI.00684-16","article-title":"HIV Maintains an Evolving and Dispersed Population in Multiple Tissues during Suppressive Combined Antiretroviral Therapy in Individuals with Cancer","volume":"90","author":"Rose","year":"2016","journal-title":"J. Virol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Tso, F.Y., Kang, G., Kwon, E.H., Julius, P., Li, Q., West, J.T., and Wood, C. (2018). Brain is a potential sanctuary for subtype C HIV-1 irrespective of ART treatment outcome. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0201325"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"172","DOI":"10.31083\/j.jin2309172","article-title":"Human Immunodeficiency Virus (HIV-1) Targets Astrocytes via Cell-Free and Cell-Associated Infection","volume":"23","author":"Susa","year":"2024","journal-title":"J. Integr. Neurosci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1111\/jnc.15336","article-title":"Astrocytes are HIV reservoirs in the brain: A cell type with poor HIV infectivity and replication but efficient cell-to-cell viral transfer","volume":"158","author":"Valdebenito","year":"2021","journal-title":"J. Neurochem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1007\/s13365-018-0691-8","article-title":"Astrocytes as an HIV CNS reservoir: Highlights and reflections of an NIMH-sponsored symposium","volume":"24","author":"Joseph","year":"2018","journal-title":"J. Neurovirol"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Lutgen, V., Narasipura, S.D., Barbian, H.J., Richards, M., Wallace, J., Razmpour, R., Buzhdygan, T., Ramirez, S.H., Prevedel, L., and Eugenin, E.A. (2020). HIV infects astrocytes in vivo and egresses from the brain to the periphery. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008381"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e00755-17","DOI":"10.1128\/JVI.00755-17","article-title":"Identification of Emerging Macrophage-Tropic HIV-1 R5 Variants in Brain Tissue of AIDS Patients without Severe Neurological Complications","volume":"91","author":"Peters","year":"2017","journal-title":"J. Virol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Moezpoor, M.R., and Stevenson, M. (2024). Help or Hinder: Protein Host Factors That Impact HIV-1 Replication. Viruses, 16.","DOI":"10.20944\/preprints202407.1995.v1"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1038\/sj.cr.7290370","article-title":"Roles of HIV-1 auxiliary proteins in viral pathogenesis and host pathogen interactions","volume":"15","author":"Li","year":"2005","journal-title":"Cell Res."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/17\/4\/467\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:59:46Z","timestamp":1760029186000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/17\/4\/467"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,25]]},"references-count":62,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["v17040467"],"URL":"https:\/\/doi.org\/10.3390\/v17040467","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,25]]}}}