{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T14:30:47Z","timestamp":1786113047291,"version":"build-2736575974"},"reference-count":104,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science and Technology Major Project for Prevention and Control of Emerging, Re-emerging and Major Infectious Diseases","award":["2025ZD01904304"],"award-info":[{"award-number":["2025ZD01904304"]}]},{"name":"National Science and Technology Major Project for Prevention and Control of Emerging, Re-emerging and Major Infectious Diseases","award":["2025ZD01905304"],"award-info":[{"award-number":["2025ZD01905304"]}]},{"name":"National Science and Technology Major Project for Prevention and Control of Emerging, Re-emerging and Major Infectious Diseases","award":["2025ZD01904500"],"award-info":[{"award-number":["2025ZD01904500"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82472268"],"award-info":[{"award-number":["82472268"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82472268"],"award-info":[{"award-number":["82472268"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010877","name":"Shenzhen Science and Technology Program","doi-asserted-by":"publisher","award":["JCYJ20240813151256072"],"award-info":[{"award-number":["JCYJ20240813151256072"]}],"id":[{"id":"10.13039\/501100010877","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shenzhen Key Laboratory of Systems Medicine for Inflammatory Diseases","award":["ZDSYS20220606100803007"],"award-info":[{"award-number":["ZDSYS20220606100803007"]}]},{"name":"National Science and Technology Major Project for Prevention and Control of Emerging, Re-emerging and Major Infectious Diseases"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Persistent HIV-1 reservoirs remain a major barrier to a durable functional cure despite long-term suppressive antiretroviral therapy. Although resting memory CD4+ T cells constitute the best-characterized cellular reservoir, tissue microenvironments shape viral persistence and immune clearance. The rectal mucosa represents a specialized tissue niche containing HIV-susceptible target cells, antigen-presenting cells, microbial products, inflammatory cues, and local metabolic signals. Within this setting, myeloid-lineage cells, particularly tissue-resident macrophages and dendritic cells, may contribute to HIV-1 persistence through mechanisms distinct from classical T-cell latency. Here, we review how rectal mucosal macrophages may support HIV-1 persistence through longevity, resistance to apoptosis, metabolic adaptation, epigenetic regulation, and sequestration of virions within virus-containing compartments. We also discuss the dual role of mucosal dendritic cells as sentinels that capture and transfer HIV-1 to CD4+ T cells, while considering the limited evidence for inducible proviral persistence in selected anatomical and cellular contexts. Importantly, we further distinguish bona fide reservoir-bearing cells from reservoir-supportive mechanisms, including viral capture, trans-infection, immune suppression, and niche-mediated protection. We also highlight how mucosal dysbiosis, barrier disruption, microbial metabolites, chronic interferon signaling, and immunoregulatory myeloid programs may stabilize HIV-1 persistence in rectal tissues. Integrating intact proviral assays, functional measurements, single-cell profiling, multiplex imaging, and spatial transcriptomics will be critical for defining myeloid-associated persistence and guiding tissue-targeted HIV-1 cure strategies.<\/jats:p>","DOI":"10.3390\/v18080858","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T16:48:08Z","timestamp":1785948488000},"page":"858","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Rectal Mucosal Myeloid Niche in HIV-1 Persistence: Reservoir Support, Viral Sequestration, and Therapeutic Opportunities"],"prefix":"10.3390","volume":"18","author":[{"given":"Hanyi","family":"Zhang","sequence":"first","affiliation":[{"name":"Key Laboratory of Tropical Disease Control of Ministry of Education, Institute of Human Virology, Department of Pathogen Biology and Biosecurity, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China"},{"name":"Shenzhen Key Laboratory for Systems Medicine in Inflammatory Diseases, Zhongshan School of Medicine, Shenzhen Campus of Sun Yat-Sen University, Sun Yat-Sen University, Shenzhen 518107, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiming","family":"Huang","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory for Systems Medicine in Inflammatory Diseases, Zhongshan School of Medicine, Shenzhen Campus of Sun Yat-Sen University, Sun Yat-Sen University, Shenzhen 518107, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Disease Control of Ministry of Education, Institute of Human Virology, Department of Pathogen Biology and Biosecurity, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7106-7312","authenticated-orcid":false,"given":"Ting","family":"Pan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Disease Control of Ministry of Education, Institute of Human Virology, Department of Pathogen Biology and Biosecurity, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China"},{"name":"Shenzhen Key Laboratory for Systems Medicine in Inflammatory Diseases, Zhongshan School of Medicine, Shenzhen Campus of Sun Yat-Sen University, Sun Yat-Sen University, Shenzhen 518107, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1038\/s41577-025-01136-7","article-title":"Immune-mediated strategies to solving the HIV reservoir problem","volume":"25","author":"Kulpa","year":"2025","journal-title":"Nat. Rev. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1038\/s41579-024-01010-8","article-title":"Immune targeting of HIV-1 reservoir cells: A path to elimination strategies and cure","volume":"22","author":"Bone","year":"2024","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1038\/s41586-022-05538-8","article-title":"Phenotypic signatures of immune selection in HIV-1 reservoir cells","volume":"614","author":"Sun","year":"2023","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"104954","DOI":"10.1016\/j.ebiom.2023.104954","article-title":"Intact proviruses are enriched in the colon and associated with PD-1(+)TIGIT(\u2212) mucosal CD4(+) T cells of people with HIV-1 on antiretroviral therapy","volume":"100","author":"Vellas","year":"2024","journal-title":"eBioMedicine"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1038\/s41564-023-01349-3","article-title":"Monocyte-derived macrophages contain persistent latent HIV reservoirs","volume":"8","author":"Veenhuis","year":"2023","journal-title":"Nat. Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"6951","DOI":"10.1038\/s41598-019-43311-6","article-title":"Distribution of Functional CD4 and CD8 T cell Subsets in Blood and Rectal Mucosal Tissues","volume":"9","author":"Amancha","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.chom.2021.01.006","article-title":"HIV-infected macrophages resist efficient NK cell-mediated killing while preserving inflammatory cytokine responses","volume":"29","author":"Clayton","year":"2021","journal-title":"Cell Host Microbe"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Buffa, D.J., O\u2019Neil, T.R., Vine, E.E., Sarkawt, L., Warner van Dijk, F.A., Dong, O.A., Nasr, N., Cunningham, A.L., Bertram, K.M., and Harman, A.N. (2025). Dendritic cells and HIV transmission: Roles and subsets of antigen-presenting cells in the human anogenital tract. PLoS Pathog., 21.","DOI":"10.1371\/journal.ppat.1013490"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Moretti, S., Schietroma, I., Sberna, G., Maggiorella, M.T., Sernicola, L., Farcomeni, S., Giovanetti, M., Ciccozzi, M., and Borsetti, A. (2023). HIV-1-Host Interaction in Gut-Associated Lymphoid Tissue (GALT): Effects on Local Environment and Comorbidities. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241512193"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1086\/656722","article-title":"Differences in HIV burden and immune activation within the gut of HIV-positive patients receiving suppressive antiretroviral therapy","volume":"202","author":"Yukl","year":"2010","journal-title":"J. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/j.immuni.2023.01.030","article-title":"HIV rapidly targets a diverse pool of CD4(+) T cells to establish productive and latent infections","volume":"56","author":"Gantner","year":"2023","journal-title":"Immunity"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"20877","DOI":"10.1073\/pnas.0911796106","article-title":"The integrin alpha4beta7 forms a complex with cell-surface CD4 and defines a T-cell subset that is highly susceptible to infection by HIV-1","volume":"106","author":"Cicala","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1007\/s11904-024-00692-2","article-title":"HIV-1 Myeloid Reservoirs-Contributors to Viral Persistence and Pathogenesis","volume":"21","author":"Ferreira","year":"2024","journal-title":"Curr. HIV\/AIDS Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1136\/gutjnl-2020-323121","article-title":"Niche-specific functional heterogeneity of intestinal resident macrophages","volume":"70","author":"Viola","year":"2021","journal-title":"Gut"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1093\/infdis\/jiae557","article-title":"Compartmentalized Human Immunodeficiency Virus Type 1 Reservoir in Intestinal Monocytes\/Macrophages on Antiretroviral Therapy","volume":"231","author":"Vellas","year":"2025","journal-title":"J. Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Wu, Y.L., Lan, G.W., Jiang, L.Y., and Chen, X. (2026). HIV Reservoirs Across Multiple Tissues: From Heterogeneous Mechanisms to Therapeutic Targeting. Microorganisms, 14.","DOI":"10.3390\/microorganisms14040844"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/s40168-022-01247-6","article-title":"Gut microbiome signatures linked to HIV-1 reservoir size and viremia control","volume":"10","author":"Borgognone","year":"2022","journal-title":"Microbiome"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.chom.2016.03.005","article-title":"Th17 Cells Are Preferentially Infected Very Early after Vaginal Transmission of SIV in Macaques","volume":"19","author":"Stieh","year":"2016","journal-title":"Cell Host Microbe"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1146\/annurev-virology-040323-082822","article-title":"Regulation of Immune Homeostasis, Inflammation, and HIV Persistence by the Microbiome, Short-Chain Fatty Acids, and Bile Acids","volume":"10","author":"Enriquez","year":"2023","journal-title":"Annu. Rev. Virol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1093\/infdis\/jiaf560","article-title":"Dissecting the Impact of the Gut Microbiome on HIV Reservoir Dynamics","volume":"233","author":"Basting","year":"2026","journal-title":"J. Infect. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1038\/s41575-023-00769-0","article-title":"Macrophages in intestinal homeostasis and inflammatory bowel disease","volume":"20","author":"Hegarty","year":"2023","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e70788","DOI":"10.1002\/jmv.70788","article-title":"Endogenous HIV-1 Tat Promotes Cell Proliferation, Migration, and Phagocytosis in Stably Infected Macrophages by Accumulating Lactate and Activating the Autophagy\/MAPK Pathway","volume":"98","author":"Na","year":"2026","journal-title":"J. Med. Virol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1111\/imr.12224","article-title":"Tissue macrophage identity and self-renewal","volume":"262","author":"Gentek","year":"2014","journal-title":"Immunol. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1038\/s41467-020-15068-4","article-title":"Perivascular localization of macrophages in the intestinal mucosa is regulated by Nr4a1 and the microbiome","volume":"11","author":"Honda","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.cell.2018.07.048","article-title":"Self-Maintaining Gut Macrophages Are Essential for Intestinal Homeostasis","volume":"175","author":"Verheijden","year":"2018","journal-title":"Cell"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Wong, M.E., Jaworowski, A., and Hearps, A.C. (2019). The HIV Reservoir in Monocytes and Macrophages. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.01435"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.1016\/j.immuni.2022.08.005","article-title":"Macrophages in the gut: Masters in multitasking","volume":"55","author":"Delfini","year":"2022","journal-title":"Immunity"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Zhang, Q., Liu, Y., Wang, X., Zhang, C., Hou, M., and Liu, Y. (2023). Integration of single-cell RNA sequencing and bulk RNA transcriptome sequencing reveals a heterogeneous immune landscape and pivotal cell subpopulations associated with colorectal cancer prognosis. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1184167"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1097\/COH.0b013e3283497203","article-title":"Macrophages and HIV-1","volume":"6","author":"Booiman","year":"2011","journal-title":"Curr. Opin. HIV AIDS"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1186\/s12964-023-01386-9","article-title":"Macrophage polarization in inflammatory bowel disease","volume":"21","author":"Zhang","year":"2023","journal-title":"Cell Commun. Signal"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e0192021","DOI":"10.1128\/mBio.01920-21","article-title":"HIV-1 Vpu Promotes Phagocytosis of Infected CD4(+) T Cells by Macrophages through Downregulation of CD47","volume":"12","author":"Cong","year":"2021","journal-title":"mBio"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1189\/jlb.0206126","article-title":"In vitro modeling of the HIV-macrophage reservoir","volume":"80","author":"Brown","year":"2006","journal-title":"J. Leukoc. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1794","DOI":"10.1016\/j.celrep.2018.04.028","article-title":"Live Imaging of HIV-1 Transfer across T Cell Virological Synapse to Epithelial Cells that Promotes Stromal Macrophage Infection","volume":"23","author":"Real","year":"2018","journal-title":"Cell Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e00092-18","DOI":"10.1128\/JVI.00092-18","article-title":"Inefficient HIV-1 trans Infection of CD4(+) T Cells by Macrophages from HIV-1 Nonprogressors Is Associated with Altered Membrane Cholesterol and DC-SIGN","volume":"92","author":"DeLucia","year":"2018","journal-title":"J. Virol."},{"key":"ref_35","first-page":"549","article-title":"Human Immunodeficiency Virus 1 (HIV-1): Viral Latency, the Reservoir, and the Cure","volume":"93","author":"Ventura","year":"2020","journal-title":"Yale J. Biol. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2584","DOI":"10.1016\/j.immuni.2023.10.002","article-title":"Single-cell epigenetic, transcriptional, and protein profiling of latent and active HIV-1 reservoir revealed that IKZF3 promotes HIV-1 persistence","volume":"56","author":"Wei","year":"2023","journal-title":"Immunity"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"24157","DOI":"10.1038\/srep24157","article-title":"Monocyte-derived macrophages exhibit distinct and more restricted HIV-1 integration site repertoire than CD4(+) T cells","volume":"6","author":"Kok","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e46916","DOI":"10.7554\/eLife.46916","article-title":"Mechanisms of virus dissemination in bone marrow of HIV-1-infected humanized BLT mice","volume":"8","author":"Ladinsky","year":"2019","journal-title":"Elife"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Moeser, M., Nielsen, J.R., and Joseph, S.B. (2020). Macrophage Tropism in Pathogenic HIV-1 and SIV Infections. Viruses, 12.","DOI":"10.3390\/v12101077"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.3390\/v6041837","article-title":"HIV-1 latency in monocytes\/macrophages","volume":"6","author":"Kumar","year":"2014","journal-title":"Viruses"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1083\/jcb.200609050","article-title":"In macrophages, HIV-1 assembles into an intracellular plasma membrane domain containing the tetraspanins CD81, CD9, and CD53","volume":"177","author":"Deneka","year":"2007","journal-title":"J. Cell Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1083\/jcb.200304008","article-title":"Infectious HIV-1 assembles in late endosomes in primary macrophages","volume":"162","author":"Kramer","year":"2003","journal-title":"J. Cell Biol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Kruize, Z., and Kootstra, N.A. (2019). The Role of Macrophages in HIV-1 Persistence and Pathogenesis. Front. Microbiol., 10.","DOI":"10.3389\/fmicb.2019.02828"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e0225223","DOI":"10.1128\/mbio.02252-23","article-title":"Gene editing of SAMHD1 in macrophage-like cells reveals complex relationships between SAMHD1 phospho-regulation, HIV-1 restriction, and cellular dNTP levels","volume":"14","author":"Schussler","year":"2023","journal-title":"mBio"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1038\/ni.2236","article-title":"SAMHD1 restricts the replication of human immunodeficiency virus type 1 by depleting the intracellular pool of deoxynucleoside triphosphates","volume":"13","author":"Lahouassa","year":"2012","journal-title":"Nat. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1002\/pro.3729","article-title":"Structural perspectives on HIV-1 Vif and APOBEC3 restriction factor interactions","volume":"29","author":"Azimi","year":"2020","journal-title":"Protein Sci."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Dicks, M.D.J., Betancor, G., Jimenez-Guardeno, J.M., Pessel-Vivares, L., Apolonia, L., Goujon, C., and Malim, M.H. (2018). Multiple components of the nuclear pore complex interact with the amino-terminus of MX2 to facilitate HIV-1 restriction. PLoS Pathog., 14.","DOI":"10.1371\/journal.ppat.1007408"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"002057","DOI":"10.1099\/jgv.0.002057","article-title":"HIV capsids: Orchestrators of innate immune evasion, pathogenesis and pandemicity","volume":"106","author":"Morling","year":"2025","journal-title":"J. Gen. Virol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"114414","DOI":"10.1016\/j.celrep.2024.114414","article-title":"Retinoic acid enhances HIV-1 reverse transcription and transcription in macrophages via mTOR-modulated mechanisms","volume":"43","author":"Dias","year":"2024","journal-title":"Cell Rep."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1126\/science.aaa7227","article-title":"GENE SILENCING. Epigenetic silencing by the HUSH complex mediates position-effect variegation in human cells","volume":"348","author":"Tchasovnikarova","year":"2015","journal-title":"Science"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e0134423","DOI":"10.1128\/mbio.01344-23","article-title":"The latent HIV reservoir: Current advances in genetic sequencing approaches","volume":"14","author":"Moar","year":"2023","journal-title":"mBio"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Pagani, I., Demela, P., Ghezzi, S., Vicenzi, E., Pizzato, M., and Poli, G. (2022). Host Restriction Factors Modulating HIV Latency and Replication in Macrophages. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23063021"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e01344-19","DOI":"10.1128\/mBio.01344-19","article-title":"Vpr Enhances HIV-1 Env Processing and Virion Infectivity in Macrophages by Modulating TET2-Dependent IFITM3 Expression","volume":"10","author":"Wang","year":"2019","journal-title":"mBio"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1919","DOI":"10.1093\/cid\/ciz108","article-title":"Naive CD4+ T Cells Harbor a Large Inducible Reservoir of Latent, Replication-competent Human Immunodeficiency Virus Type 1","volume":"69","author":"Zerbato","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1097\/COH.0000000000000851","article-title":"The multifaceted nature of HIV tissue reservoirs","volume":"19","author":"Banga","year":"2024","journal-title":"Curr. Opin. HIV AIDS"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1016\/j.mucimm.2023.06.006","article-title":"Metabolic adaption of mucosal macrophages: Is metabolism a driver of persistence across tissues?","volume":"16","author":"Bennett","year":"2023","journal-title":"Mucosal Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/1476-511X-11-69","article-title":"Retinoic acid and liver X receptor agonist synergistically inhibit HIV infection in CD4+ T cells by up-regulating ABCA1-mediated cholesterol efflux","volume":"11","author":"Jiang","year":"2012","journal-title":"Lipids Health Dis."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e187663","DOI":"10.1172\/JCI187663","article-title":"The macrophage-intrinsic MDA5\/IRF5 axis drives HIV-1 intron-containing RNA-induced inflammatory responses","volume":"135","author":"Ramaswamy","year":"2025","journal-title":"J. Clin. Invest."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Jin, J., Xu, Q., Zhang, X., Zhu, A., Xia, W., Moog, C., Chan, A.S.W., Zhang, T., and Su, B. (2025). HIV infection and immunosenescence: Challenges and intervention strategies. BMC Med., 24.","DOI":"10.1186\/s12916-025-04545-6"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1016\/j.immuni.2022.03.004","article-title":"Single-cell multiomics reveals persistence of HIV-1 in expanded cytotoxic T cell clones","volume":"55","author":"Collora","year":"2022","journal-title":"Immunity"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"105947","DOI":"10.1016\/j.antiviral.2024.105947","article-title":"KDM5A\/B contribute to HIV-1 latent infection and survival of HIV-1 infected cells","volume":"228","author":"Li","year":"2024","journal-title":"Antivir. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"3691","DOI":"10.1038\/s41467-021-24087-8","article-title":"Vpr counteracts the restriction of LAPTM5 to promote HIV-1 infection in macrophages","volume":"12","author":"Zhao","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Mohamed, H., Gurrola, T., Berman, R., Collins, M., Sariyer, I.K., Nonnemacher, M.R., and Wigdahl, B. (2021). Targeting CCR5 as a Component of an HIV-1 Therapeutic Strategy. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.816515"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"eabe1707","DOI":"10.1126\/science.abe1707","article-title":"CARD8 is an inflammasome sensor for HIV-1 protease activity","volume":"371","author":"Wang","year":"2021","journal-title":"Science"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2928","DOI":"10.1016\/j.immuni.2024.11.002","article-title":"Cognate antigen engagement induces HIV-1 expression in latently infected CD4(+) T cells from people on long-term antiretroviral therapy","volume":"57","author":"Moskovljevic","year":"2024","journal-title":"Immunity"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1186\/s43556-025-00300-8","article-title":"Dendritic cells: Understanding ontogeny, subsets, functions, and their clinical applications","volume":"6","author":"Li","year":"2025","journal-title":"Mol. BioMed."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1146\/annurev-virology-020520-025625","article-title":"Mucosal Dendritic Cell Subsets Control HIV-1\u2032s Viral Fitness","volume":"7","author":"Nijmeijer","year":"2020","journal-title":"Annu. Rev. Virol."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Man, S., Jansen, J., Kootstra, N.A., and Geijtenbeek, T.B.H. (2026). Transcriptomic Signatures of Immune Suppression and Cellular Dysfunction Distinguish Latent from Transcriptionally Active HIV-1 Infection in Dendritic Cells. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27020844"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.molmed.2007.11.001","article-title":"Distinct roles for DC-SIGN+-dendritic cells and Langerhans cells in HIV-1 transmission","volume":"14","author":"Nabatov","year":"2008","journal-title":"Trends Mol. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"4225","DOI":"10.1021\/acs.jmedchem.4c00116","article-title":"Glycan-Modified Peptides for Dual Inhibition of Human Immunodeficiency Virus Entry into Dendritic Cells and T Cells","volume":"67","author":"Cheng","year":"2024","journal-title":"J. Med. Chem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2147","DOI":"10.1038\/s41467-021-22375-x","article-title":"Human anogenital monocyte-derived dendritic cells and langerin+cDC2 are major HIV target cells","volume":"12","author":"Rhodes","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/nm1541","article-title":"Langerin is a natural barrier to HIV-1 transmission by Langerhans cells","volume":"13","author":"Nabatov","year":"2007","journal-title":"Nat. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1093\/infdis\/jiae013","article-title":"Magnitude of Type I Interferon Responses by Plasmacytoid Dendritic Cells After TLR7 Stimulation Is Associated With Human Immunodeficiency Virus Type 1 (HIV-1) Reservoir Sizes in Cisgender Women With HIV-1 on Antiretroviral Therapy","volume":"229","author":"Thiele","year":"2024","journal-title":"J. Infect. Dis."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"eabm9409","DOI":"10.1126\/sciimmunol.abm9409","article-title":"Human dendritic cells in cancer","volume":"7","author":"Kvedaraite","year":"2022","journal-title":"Sci. Immunol."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Martin-Gayo, E., and Yu, X.G. (2019). Role of Dendritic Cells in Natural Immune Control of HIV-1 Infection. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.01306"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"e1923","DOI":"10.1002\/rmv.1923","article-title":"Langerhans cells and sexual transmission of HIV and HSV","volume":"27","author":"Botting","year":"2017","journal-title":"Rev. Med. Virol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1186\/s12977-016-0323-4","article-title":"Are T cells the only HIV-1 reservoir?","volume":"13","author":"Kandathil","year":"2016","journal-title":"Retrovirology"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Dodagatta-Marri, E., Mitchell, D.A., Pandit, H., Sonawani, A., Murugaiah, V., Idicula-Thomas, S., Nal, B., Al-Mozaini, M.M., Kaur, A., and Madan, T. (2017). Protein-Protein Interaction between Surfactant Protein D and DC-SIGN via C-Type Lectin Domain Can Suppress HIV-1 Transfer. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.00834"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1016\/j.cell.2015.12.036","article-title":"Actin Dynamics Regulates Dendritic Cell-Mediated Transfer of HIV-1 to T Cells","volume":"164","author":"Menager","year":"2016","journal-title":"Cell"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.chom.2016.02.016","article-title":"Actin\u2019 on HIV: How Dendritic Cells Spread Infection","volume":"19","author":"Donahue","year":"2016","journal-title":"Cell Host Microbe"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Warner van Dijk, F.A., Bertram, K.M., O\u2019Neil, T.R., Li, Y., Buffa, D.J., Harman, A.N., Cunningham, A.L., and Nasr, N. (2025). Recent Advances in Our Understanding of Human Inflammatory Dendritic Cells in Human Immunodeficiency Virus Infection. Viruses, 17.","DOI":"10.3390\/v17010105"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Lehmann, C., Lafferty, M., Garzino-Demo, A., Jung, N., Hartmann, P., Fatkenheuer, G., Wolf, J.S., van Lunzen, J., and Romerio, F. (2010). Plasmacytoid dendritic cells accumulate and secrete interferon alpha in lymph nodes of HIV-1 patients. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0011110"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"20627","DOI":"10.1038\/s41598-025-04613-0","article-title":"Increased IFN responses drive myeloid cell activation in people living with HIV-1","volume":"15","author":"Placais","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1714","DOI":"10.1016\/j.chom.2023.08.020","article-title":"Lymph node dendritic cells harbor inducible replication-competent HIV despite years of suppressive ART","volume":"31","author":"Banga","year":"2023","journal-title":"Cell Host Microbe"},{"key":"ref_85","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. Invest."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"N\u00fchn, M.M., Gumbs, S.B.H., Schipper, P.J., Drosou, I., Gharu, L., Buchholtz, N., Snijders, G., Gigase, F.A.J., Wensing, A.M.J., and Symons, J. (2025). Microglia Exhibit a Unique Intact HIV Reservoir in Human Postmortem Brain Tissue. Viruses, 17.","DOI":"10.3390\/v17040467"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/s41577-021-00649-1","article-title":"Engaging innate immunity in HIV-1 cure strategies","volume":"22","author":"Board","year":"2022","journal-title":"Nat. Rev. Immunol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"164203","DOI":"10.1155\/2013\/164203","article-title":"HIV-1 Trans Infection of CD4(+) T Cells by Professional Antigen Presenting Cells","volume":"2013","author":"Rinaldo","year":"2013","journal-title":"Scientifica"},{"key":"ref_89","first-page":"3","article-title":"Targeting the pDC\/IFN-I axis in HIV-1 immunotherapy","volume":"21","author":"Su","year":"2026","journal-title":"Curr. Opin. HIV AIDS"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1097\/COH.0000000000000836","article-title":"Targeting HIV persistence in the tissue","volume":"19","author":"Pieren","year":"2024","journal-title":"Curr. Opin. HIV AIDS"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1097\/COH.0000000000000961","article-title":"Roadmap for spatial transcriptomics of HIV in tissues","volume":"20","author":"Guan","year":"2025","journal-title":"Curr. Opin. HIV AIDS"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1186\/s40364-024-00658-x","article-title":"Single cell spatial profiling of FFPE splenic tissue from a humanized mouse model of HIV infection","volume":"12","author":"Wu","year":"2024","journal-title":"Biomark. Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1038\/s41467-022-28727-5","article-title":"First-in-human immunoPET imaging of HIV-1 infection using (89)Zr-labeled VRC01 broadly neutralizing antibody","volume":"13","author":"Flavell","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.chom.2017.12.004","article-title":"Getting the \u201cKill\u201d into \u201cShock and Kill\u201d: Strategies to Eliminate Latent HIV","volume":"23","author":"Kim","year":"2018","journal-title":"Cell Host Microbe"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"106733","DOI":"10.1016\/j.jinf.2026.106733","article-title":"Selective elimination of myeloid HIV reservoirs by targeting pro-survival pathways","volume":"92","author":"Li","year":"2026","journal-title":"J. Infect."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"e00755-20","DOI":"10.1128\/JVI.00755-20","article-title":"Combination of CD8beta Depletion and Interleukin-15 Superagonist N-803 Induces Virus Reactivation in Simian-Human Immunodeficiency Virus-Infected, Long-Term ART-Treated Rhesus Macaques","volume":"94","author":"McBrien","year":"2020","journal-title":"J. Virol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1038\/s41586-020-1946-0","article-title":"Robust and persistent reactivation of SIV and HIV by N-803 and depletion of CD8(+) cells","volume":"578","author":"McBrien","year":"2020","journal-title":"Nature"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1038\/s41591-021-01651-9","article-title":"Safety and virologic impact of the IL-15 superagonist N-803 in people living with HIV: A phase 1 trial","volume":"28","author":"Miller","year":"2022","journal-title":"Nat. Med."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Vansant, G., Bruggemans, A., Janssens, J., and Debyser, Z. (2020). Block-And-Lock Strategies to Cure HIV Infection. Viruses, 12.","DOI":"10.3390\/v12010084"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1186\/s12951-022-01539-x","article-title":"Mucus interaction to improve gastrointestinal retention and pharmacokinetics of orally administered nano-drug delivery systems","volume":"20","author":"Subramanian","year":"2022","journal-title":"J. Nanobiotechnology"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"45302","DOI":"10.1038\/s41598-025-29002-5","article-title":"Enhancing antiretroviral delivery to secondary lymph nodes by targeting CD169 + macrophages with HIV-mimicking nanoparticles","volume":"15","author":"Fofana","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jconrel.2018.08.014","article-title":"Macrophage-targeted drugamers with enzyme-cleavable linkers deliver high intracellular drug dosing and sustained drug pharmacokinetics against alveolar pulmonary infections","volume":"287","author":"Su","year":"2018","journal-title":"J. Control Release"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1093\/jac\/dkaa523","article-title":"Pharmacokinetic\/pharmacodynamic analysis of romidepsin used as an HIV latency reversing agent","volume":"76","author":"Molto","year":"2021","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Zou, H., Banerjee, P., Leung, S.S.Y., and Yan, X. (2020). Application of Pharmacokinetic-Pharmacodynamic Modeling in Drug Delivery: Development and Challenges. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.00997"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/18\/8\/858\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T16:49:55Z","timestamp":1785948595000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/18\/8\/858"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,5]]},"references-count":104,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["v18080858"],"URL":"https:\/\/doi.org\/10.3390\/v18080858","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,5]]}}}