{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T18:19:01Z","timestamp":1783707541024,"version":"3.55.0"},"reference-count":99,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"121","funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI005157-01"],"award-info":[{"award-number":["AI005157-01"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017540","name":"NHLBI Division of Intramural Research","doi-asserted-by":"publisher","award":["ZIA\/hl1006223"],"award-info":[{"award-number":["ZIA\/hl1006223"]}],"id":[{"id":"10.13039\/100017540","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institutes of Health Extramural Research Program MK","award":["R35GM138283"],"award-info":[{"award-number":["R35GM138283"]}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Immunol."],"published-print":{"date-parts":[[2026,7,10]]},"abstract":"<jats:p>\n                    CD46, a human-specific complement receptor, regulates gene programs essential for T helper 1 (T\n                    <jats:sub>H<\/jats:sub>\n                    1) cell differentiation, yet how it exerts direct transcriptional control remains unclear. We show that the CD46 signaling domain cytoplasmic tail 1 (CYT-1) engages the transcription factor Sp1 in human CD4 T cells to dynamically modulate Sp1-DNA interactions. Beyond promoting T\n                    <jats:sub>H<\/jats:sub>\n                    1 cell induction, CD46-Sp1\u2013controlled programs support naive CD4 T cell survival by maintaining nutrient transporter expression and suppressing the intrinsic caspase 9\u2013caspase 3 apoptotic pathway. The CD46-Sp1 axis also restrains HIV transcription in infected CD4 T cells in vitro. Disruption of CYT-1\u2013Sp1\u2013regulated programs identifies T cells from individuals with HIV who exhibit incomplete viral suppression during antiretroviral therapy. Together, these findings define a human-specific transcriptional mechanism linking complement signaling to metabolic adaptation, apoptosis regulation, and antiviral defense, highlighting an unexpected role for CD46 in coordinating T cell homeostasis and host protection.\n                  <\/jats:p>","DOI":"10.1126\/sciimmunol.aeb5857","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T17:58:24Z","timestamp":1783706304000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Sp1 links CD46 to CD4 T cell metabolic fitness, survival, and retroviral control"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3568-0619","authenticated-orcid":true,"given":"Parul","family":"Singh","sequence":"first","affiliation":[{"name":"Complement and Inflammation Research Section, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5758-4092","authenticated-orcid":true,"given":"Luopin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Computer Science, Purdue University, West Lafayette, IN, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavitra","family":"Ramdas","sequence":"additional","affiliation":[{"name":"Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0522-3353","authenticated-orcid":true,"given":"Shyaman M.","family":"Jayasundara","sequence":"additional","affiliation":[{"name":"Department of Computer Science, Purdue University, West Lafayette, IN, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2051-3829","authenticated-orcid":true,"given":"Gaelle","family":"Le Friec","sequence":"additional","affiliation":[{"name":"UCB, Slough, Berkshire, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6583-360X","authenticated-orcid":true,"given":"Natalia","family":"Kunz","sequence":"additional","affiliation":[{"name":"Complement and Inflammation Research Section, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prakriti","family":"Mudvari","sequence":"additional","affiliation":[{"name":"Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7103-8394","authenticated-orcid":true,"given":"Erin E.","family":"West","sequence":"additional","affiliation":[{"name":"Complement and Inflammation Research Section, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9027-6339","authenticated-orcid":true,"given":"Ayden","family":"Case","sequence":"additional","affiliation":[{"name":"Complement and Inflammation Research Section, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD, USA."},{"name":"Heart and Lung Research Institute, University of Cambridge, Cambridge, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0379-7724","authenticated-orcid":true,"given":"Nicolas S.","family":"Merle","sequence":"additional","affiliation":[{"name":"Complement and Inflammation Research Section, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack A.","family":"Bibby","sequence":"additional","affiliation":[{"name":"Complement and Inflammation Research Section, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Hasle","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4633-4594","authenticated-orcid":true,"given":"Eli A.","family":"Boritz","sequence":"additional","affiliation":[{"name":"Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7080-8820","authenticated-orcid":true,"given":"Majid","family":"Kazemian","sequence":"additional","affiliation":[{"name":"Department of Computer Science, Purdue University, West Lafayette, IN, USA."},{"name":"Purdue Institute for Cancer Research, Purdue University, West Lafayette, IN, USA."},{"name":"Department of Biochemistry, Purdue University, West Lafayette, IN, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4196-1417","authenticated-orcid":true,"given":"Claudia","family":"Kemper","sequence":"additional","affiliation":[{"name":"Complement and Inflammation Research Section, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","first-page":"45","article-title":"Membrane cofactor protein","volume":"178","author":"Liszewski M. K.","year":"1992","unstructured":"M. K. Liszewski, J. P. Atkinson, Membrane cofactor protein. Curr. Top. Microbiol. Immunol. 178, 45\u201360 (1992).","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2021.04.005"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.6.2161"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1997.4841857.x"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.9.4385-4388.2004"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.9.5143"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2018.06.030"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0039.2004.00277.x"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2011.06.003"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.10.018"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200109005"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.12.6780"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01315"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2013.11.010"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2454"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.05.024"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2023.07.014"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06706-z"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1917"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2016.12.027"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells10113094"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12920-020-0680-7"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3300163"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1900527"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2007-8-2-r24"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M103968200"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2015.05.008"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2003-4-2-206"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-183X.2006.00256.x"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2015.10.005"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1111\/febs.13148"},{"key":"e_1_3_2_33_2","first-page":"513","article-title":"The role of the ubiquitously expressed transcription factor Sp1 in tissue-specific transcriptional regulation and in disease","volume":"89","author":"O\u2019Connor L.","year":"2016","unstructured":"L. O\u2019Connor, J. Gilmour, C. Bonifer, The role of the ubiquitously expressed transcription factor Sp1 in tissue-specific transcriptional regulation and in disease. Yale J. Biol. Med. 89, 513\u2013525 (2016).","journal-title":"Yale J. Biol. Med."},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.4.1839"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12852"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-021-01328-8"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.174.1.93"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506580102"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-08332-9"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad1210"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2007.12.1171"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/377348a0"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.5.3323"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2008.03040.x"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-025-02176-0"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-042617-053019"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.115199"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.04.037"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1003968"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1111\/imm.12655"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2014.216"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.11.044"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.9.5425"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.190.12.1879"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22020817"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0955-0674(02)00384-8"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-025-01470-9"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1042\/BCJ20210724"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1770-6"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401950"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.916347"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2025.118493"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2009.09.006"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2010.09.016"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2019.1695398"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI191119"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1993.tb06029.x"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.3390\/v12050495"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115474"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2023.10.002"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virs.2023.03.001"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.08.003"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111697"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.05.016"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1994.tb06695.x"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep35406"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2022.03.004"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciz108"},{"key":"e_1_3_2_79_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI188533"},{"key":"e_1_3_2_80_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.133157"},{"key":"e_1_3_2_81_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2020.101438"},{"key":"e_1_3_2_82_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells14050351"},{"key":"e_1_3_2_83_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05556-6"},{"key":"e_1_3_2_84_2","doi-asserted-by":"publisher","DOI":"10.1097\/COH.0b013e32834086ce"},{"key":"e_1_3_2_85_2","doi-asserted-by":"crossref","unstructured":"S. L. Quinn M. George J. D. Ventura E. J. Fray M. Aid V. E. K. Walker-Sperling J. D. Siliciano R. F. Siliciano S. Nguyen D. H. Barouch A. K. Shalek Longitudinal transcriptomic analysis of SIV-infected rhesus macaques reveals peripheral immune dynamics throughout untreated SIV infection and long-term antiretroviral therapy. bioRxiv 669172 [Preprint] (2025); https:\/\/doi.org\/10.1101\/2025.08.08.669172.","DOI":"10.1101\/2025.08.08.669172"},{"key":"e_1_3_2_86_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M414134200"},{"key":"e_1_3_2_87_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.21856"},{"key":"e_1_3_2_88_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1923"},{"key":"e_1_3_2_89_2","doi-asserted-by":"publisher","DOI":"10.1093\/gigascience\/giab008"},{"key":"e_1_3_2_90_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw257"},{"key":"e_1_3_2_91_2","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2008-9-9-r137"},{"key":"e_1_3_2_92_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq033"},{"key":"e_1_3_2_93_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv416"},{"key":"e_1_3_2_94_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2010.05.004"},{"key":"e_1_3_2_95_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1754"},{"key":"e_1_3_2_96_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-12-323"},{"key":"e_1_3_2_97_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp616"},{"key":"e_1_3_2_98_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2009.01.002"},{"key":"e_1_3_2_99_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02124-20"},{"key":"e_1_3_2_100_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.00166-23"}],"container-title":["Science Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciimmunol.aeb5857","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T17:58:26Z","timestamp":1783706306000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciimmunol.aeb5857"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,10]]},"references-count":99,"journal-issue":{"issue":"121","published-print":{"date-parts":[[2026,7,10]]}},"alternative-id":["10.1126\/sciimmunol.aeb5857"],"URL":"https:\/\/doi.org\/10.1126\/sciimmunol.aeb5857","relation":{},"ISSN":["2470-9468"],"issn-type":[{"value":"2470-9468","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,10]]},"assertion":[{"value":"2025-08-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-07","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eaeb5857"}}