{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T13:29:03Z","timestamp":1787059743031,"version":"build-2736575974"},"reference-count":54,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["09150162010163"],"award-info":[{"award-number":["09150162010163"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["09120232310030"],"award-info":[{"award-number":["09120232310030"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016036","name":"Health~Holland","doi-asserted-by":"crossref","award":["LSHM19101\/P-44802"],"award-info":[{"award-number":["LSHM19101\/P-44802"]}],"id":[{"id":"10.13039\/100016036","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100016036","name":"Health~Holland","doi-asserted-by":"crossref","award":["KWF PPS VU2022-14453"],"award-info":[{"award-number":["KWF PPS VU2022-14453"]}],"id":[{"id":"10.13039\/100016036","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004622","name":"Dutch Cancer Society","doi-asserted-by":"crossref","award":["VU2019-12802,2025-AF-1 \/ 17146"],"award-info":[{"award-number":["VU2019-12802,2025-AF-1 \/ 17146"]}],"id":[{"id":"10.13039\/501100004622","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007553","name":"Aids Fonds","doi-asserted-by":"publisher","award":["LSHM19101\/P-44802"],"award-info":[{"award-number":["LSHM19101\/P-44802"]}],"id":[{"id":"10.13039\/100007553","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016036","name":"Health~Holland","doi-asserted-by":"crossref","award":["2019-1167"],"award-info":[{"award-number":["2019-1167"]}],"id":[{"id":"10.13039\/100016036","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2026,8,18]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Human immunodeficiency virus 1 (HIV-1) remains a global health burden affecting over 39 million people worldwide, with approximately one million new infections occurring each year. Sexual transmission remains the predominant route of HIV-1 acquisition, during which the virus crosses mucosal barriers and interacts with host immune cells to facilitate infection. Dendritic cells (DCs) contribute to systemic viral spread and seeding of reservoirs by efficiently capturing HIV-1, leading to infection and subsequent transmission of the virus to CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells. Siglec-1 (CD169) is a key receptor involved in HIV-1 capture, and its blockade may help prevent viral transmission. Here, we used newly developed single-domain antibodies, also known as nanobodies, against Siglec-1 as a candidate inhibitor to limit HIV-1 transmission. Using a Siglec-1-overexpressing cell line, we demonstrated that these nanobodies specifically blocked Siglec-1-mediated HIV-1 binding and transmission. Extending these findings to a more physiologically relevant context, the anti-Siglec-1 nanobodies neither induced immune nor cellular activation in DCs, indicating a favorable safety profile for functional applications. Most notably, the anti-Siglec-1 nanobody 2C2 effectively blocked HIV-1 binding as well as infection of DCs. Moreover, both replication-dependent and replication-independent HIV-1 transmission by DCs was also abrogated by the nanobody. Our findings not only underscore the relevance of Siglec-1 in HIV-1 capture but also highlight the therapeutic potential of utilizing host-targeting strategies against infectious diseases.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>Sexual transmission is the main route of human immunodeficiency virus 1 (HIV-1) infection, and novel interventions are needed to prevent this crucial first step. Mucosal dendritic cells play a key role by capturing HIV-1 via attachment receptors, leading to dendritic cell infection and subsequent transmission to T cells, thereby facilitating viral spread and establishment of infection. Here, we show that small, highly specific nanobodies targeting the attachment receptor Siglec-1 strongly interfere with this early stage of HIV-1 transmission. Siglec-1 nanobodies prevented HIV-1 binding to and infection of dendritic cells, thereby blocking transmission to T cells without inducing unwanted immune activation. Together, these findings identify Siglec-1 nanobodies as promising interventions and support the development of host-directed nanobody-based strategies to reduce HIV-1 spread.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.00128-26","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T13:00:19Z","timestamp":1785330019000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Siglec-1-targeted nanobodies restrict HIV-1 transmission and infection of dendritic cells"],"prefix":"10.1128","volume":"100","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-0933-2564","authenticated-orcid":true,"given":"Shirley","family":"Man","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05grdyy37","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Experimental Immunology, Amsterdam UMC Location AMC","place":["Amsterdam, the Netherlands"]},{"name":"Amsterdam Institute for Immunology and Infectious Diseases","place":["Amsterdam, the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alsya J.","family":"Affandi","sequence":"additional","affiliation":[{"name":"Amsterdam Institute for Immunology and Infectious Diseases","place":["Amsterdam, the Netherlands"]},{"id":[{"id":"https:\/\/ror.org\/00q6h8f30","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Cell Biology and Immunology, Amsterdam UMC location VUmc","place":["Amsterdam, the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hendrik J.","family":"Brink","sequence":"additional","affiliation":[{"name":"Amsterdam Institute for Immunology and Infectious Diseases","place":["Amsterdam, the Netherlands"]},{"id":[{"id":"https:\/\/ror.org\/00q6h8f30","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Cell Biology and Immunology, Amsterdam UMC location VUmc","place":["Amsterdam, the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John L.","family":"van Hamme","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05grdyy37","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Experimental Immunology, Amsterdam UMC Location AMC","place":["Amsterdam, the Netherlands"]},{"name":"Amsterdam Institute for Immunology and Infectious Diseases","place":["Amsterdam, the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronique A. L.","family":"Konijn","sequence":"additional","affiliation":[{"name":"Amsterdam Institute for Immunology and Infectious Diseases","place":["Amsterdam, the Netherlands"]},{"id":[{"id":"https:\/\/ror.org\/00q6h8f30","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Cell Biology and Immunology, Amsterdam UMC location VUmc","place":["Amsterdam, the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joeke G. C.","family":"Stolwijk","sequence":"additional","affiliation":[{"name":"Amsterdam Institute for Immunology and Infectious Diseases","place":["Amsterdam, the Netherlands"]},{"id":[{"id":"https:\/\/ror.org\/00q6h8f30","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Cell Biology and Immunology, Amsterdam UMC location VUmc","place":["Amsterdam, the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joke M. M.","family":"den Haan","sequence":"additional","affiliation":[{"name":"Amsterdam Institute for Immunology and Infectious Diseases","place":["Amsterdam, the Netherlands"]},{"id":[{"id":"https:\/\/ror.org\/00q6h8f30","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Cell Biology and Immunology, Amsterdam UMC location VUmc","place":["Amsterdam, the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9429-7754","authenticated-orcid":true,"given":"Neeltje A.","family":"Kootstra","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05grdyy37","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Experimental Immunology, Amsterdam UMC Location AMC","place":["Amsterdam, the Netherlands"]},{"name":"Amsterdam Institute for Immunology and Infectious Diseases","place":["Amsterdam, the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5710-2839","authenticated-orcid":true,"given":"Teunis B. H.","family":"Geijtenbeek","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05grdyy37","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Experimental Immunology, Amsterdam UMC Location AMC","place":["Amsterdam, the Netherlands"]},{"name":"Amsterdam Institute for Immunology and Infectious Diseases","place":["Amsterdam, the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","volume-title":"Global HIV & AIDS statistics \u2013 2024 fact sheet","author":"HIV\/AIDS JUNPo","year":"2024","unstructured":"HIV\/AIDS JUNPo. 2024. Global HIV & AIDS statistics \u2013 2024 fact sheet. UNAIDS, Geneva."},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2443-1"},{"key":"e_1_3_4_4_2","volume-title":"2024 global AIDS report \u2014 the urgency of now: AIDS at a crossroads","author":"HIV\/AIDS JUNPo","year":"2024","unstructured":"HIV\/AIDS JUNPo. 2024. 2024 global AIDS report \u2014 the urgency of now: AIDS at a crossroads. UNAIDS, Geneva."},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.71.5.4016-4023.1997"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.183.1.215"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0897.2010.00939.x"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1352913"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0092-8674(00)80694-7"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-09-3129"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1003040107"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2020.101427"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.72.10.7822-7829.1998"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00825"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003291"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12977-015-0160-x"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1001448"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0001967"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3737"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines13030330"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1201104109"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1001315"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-019-0453-2"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-021-00794-6"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004751"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.78836"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1911007116"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2023.106019"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","unstructured":"Brink HJ Affandi AJ Man S Dekker N Gro\u00dfe Wichtrup EA Bouma RG Seyed Toutounchi N Konijn VAL Stolwijk JGC van Hamme JL Olesek K Heijnen DAM Fish A Moutsiopoulou A Celie PHN Dekkers G Heukers R Mastrobattista E Smit MJ van Kooyk Y Heikema AP Kootstra NA Geijtenbeek TBH den Haan JMM. 2025. Identification of allo- or orthosteric VHH\/single-domain antibodies that enhance or block pathogen binding to Siglec-1 on dendritic cells. bioRxiv. doi:10.64898\/2025.12.19.695420","DOI":"10.64898\/2025.12.19.695420"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.2.1145"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2006186117"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep00763"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2008.01.007"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coviro.2011.10.006"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3787"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000134"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.16.9267"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/s1097-2765(00)80071-4"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.v97.1.288"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1505840"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2015.108"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.721258"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0024559"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.2A0815-361R"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0189945"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0703747104"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni841"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1089\/AID.2015.0235"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006181"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-024-02900-y"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1039\/c9md00018f"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12412"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.01.021"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2018.11.011"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2024.116726"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/jvi.00128-26","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/jvi.00128-26","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T13:05:19Z","timestamp":1787058319000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/jvi.00128-26"}},"subtitle":[],"editor":[{"given":"Daniel","family":"Sauter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,8,18]]},"references-count":54,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8,18]]}},"alternative-id":["10.1128\/jvi.00128-26"],"URL":"https:\/\/doi.org\/10.1128\/jvi.00128-26","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,18]]},"assertion":[{"value":"2026-01-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00128-26"}}