{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:05:48Z","timestamp":1792785948426,"version":"4.5.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Africa Health Research Institute","award":["227167\/A\/23\/Z"],"award-info":[{"award-number":["227167\/A\/23\/Z"]}],"id":[{"id":"https:\/\/ror.org\/034m6ke32","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI145305"],"award-info":[{"award-number":["R01AI145305"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI181690"],"award-info":[{"award-number":["R01AI181690"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Dan and Marjorie Sullivan Research Scholar 97 Award","award":["224910"],"award-info":[{"award-number":["224910"]}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["INV-027090"],"award-info":[{"award-number":["INV-027090"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["INV-045620"],"award-info":[{"award-number":["INV-045620"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["INV-050722"],"award-info":[{"award-number":["INV-050722"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["INV-065242"],"award-info":[{"award-number":["INV-065242"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Antiretroviral therapy effectively suppresses human immunodeficiency virus 1 (HIV-1) replication in blood but fails to eradicate viral reservoirs in lymphoid tissues, particularly in germinal centers (GCs) of lymph nodes (LNs). While CD8+ T cells are largely excluded from GCs, the role of natural killer (NK) cells, potential alternative effectors, remains poorly defined in human LNs during HIV infection. We investigated NK-cell phenotype, function, and localization in paired LN and peripheral blood samples from South African women with HIV (WWH) and HIV-negative controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using immunofluorescence microscopy, flow cytometry, and spatial analysis, we characterized NK-cell subsets, assessed CXCR5 expression, and mapped their distribution relative to HIV-infected GC regions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Natural killer cells displayed distinct compartmentalized phenotypes, with CD56+CD16+ cells enriched in blood and CD56+CD16\u2212 cells predominating in LNs, irrespective of HIV status. Within LNs, NK cells were largely excluded from GCs and localized to the extrafollicular and mantle zones. CXCR5+ NK cells, with follicular homing potential, were rare across all donors and not enriched in WWH. Natural killer\u2013cell cytolytic activity was predominantly restricted to CXCR5\u2212 subsets outside follicles during viremia, despite elevated granzyme B expression. Spatial modeling confirmed NK-cell segregation from HIV-infected GC regions, limiting their antiviral potential.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Lymph node\u2013resident NK cells are functionally and spatially constrained during HIV infection, highlighting a disconnect between NK-cell effector capacity and the localization of the HIV reservoir. Enhancing NK-cell trafficking or function within lymphoid tissues may therefore represent a promising avenue for HIV remission or cure strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/infdis\/jiag446","type":"journal-article","created":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T11:42:44Z","timestamp":1789213364000},"source":"Crossref","is-referenced-by-count":0,"title":["Spatial Constraints Limit Natural Killer Cell Access to Germinal Center HIV Reservoirs in Lymph Nodes"],"prefix":"10.1093","author":[{"given":"Mali","family":"Mlaba","sequence":"first","affiliation":[{"name":"Africa Health Research Institute , Durban, KwaZulu-Natal ,","place":["South Africa"]},{"name":"HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Umbilo , Durban ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Namani","family":"Ngema","sequence":"additional","affiliation":[{"name":"Africa Health Research Institute , Durban, KwaZulu-Natal ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thandekile","family":"Ngubane","sequence":"additional","affiliation":[{"name":"Department of Surgery, Prince Mshiyeni Memorial Hospital, Umlazi , Durban ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trevor","family":"Khaba","sequence":"additional","affiliation":[{"name":"HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Umbilo , Durban ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0906-808X","authenticated-orcid":false,"given":"Merantha","family":"Moodley","sequence":"additional","affiliation":[{"name":"Africa Health Research Institute , Durban, KwaZulu-Natal ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5554-4318","authenticated-orcid":false,"given":"Crystal A","family":"Mendoza","sequence":"additional","affiliation":[{"name":"Ragon Institute of Massachussetts General Hospital, Massachussetts Institute of Technology, and Harvard , Cambridge, Massachusetts ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Pansegrouw","sequence":"additional","affiliation":[{"name":"Department of Surgery, Prince Mshiyeni Memorial Hospital, Umlazi , Durban ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2708-3315","authenticated-orcid":false,"given":"Zaza M","family":"Ndhlovu","sequence":"additional","affiliation":[{"name":"Africa Health Research Institute , Durban, KwaZulu-Natal ,","place":["South Africa"]},{"name":"HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Umbilo , Durban ,","place":["South Africa"]},{"name":"Ragon Institute of Massachussetts General Hospital, Massachussetts Institute of Technology, and Harvard , Cambridge, Massachusetts ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"key":"2026092312000621800_jiag446-B1","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1038\/387183a0","article-title":"Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection","volume":"387","author":"Chun","year":"1997","journal-title":"Nature"},{"key":"2026092312000621800_jiag446-B2","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1038\/8394","article-title":"Latent infection of CD4+ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination 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