{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T16:31:12Z","timestamp":1793377872499,"version":"4.5.0"},"reference-count":88,"publisher":"Elsevier BV","issue":"10","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100007046","name":"Wuhan University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007046","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010888","name":"Wuhan Science and Technology Bureau","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010888","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of the People's Republic of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007162","name":"Department of Science and Technology of Guangdong Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007162","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Guangdong Provincial Natural Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Therapy"],"published-print":{"date-parts":[[2026,10]]},"DOI":"10.1016\/j.ymthe.2026.07.048","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T16:10:58Z","timestamp":1785341458000},"page":"6039-6059","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synchronized latency reversal and immune clearance by a multifunctional fusion protein enables HIV-1 reservoir reduction"],"prefix":"10.1016","volume":"34","author":[{"given":"Fei","family":"Luo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinghui","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjia","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajun","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqing","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongmei","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangyang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyang","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Qian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shicheng","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhida","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tielong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shihui","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linghua","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haisheng","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0669-5037","authenticated-orcid":false,"given":"Liang","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ymthe.2026.07.048_bib1","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1016\/j.immuni.2018.04.030","article-title":"Targeting the Latent Reservoir for HIV-1","volume":"48","author":"Sengupta","year":"2018","journal-title":"Immunity"},{"key":"10.1016\/j.ymthe.2026.07.048_bib2","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.chom.2020.03.014","article-title":"The Biology of the HIV-1 Latent Reservoir and Implications for Cure Strategies","volume":"27","author":"Cohn","year":"2020","journal-title":"Cell Host Microbe"},{"key":"10.1016\/j.ymthe.2026.07.048_bib3","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1056\/NEJM199905273402101","article-title":"Quantifying residual HIV-1 replication in patients receiving combination antiretroviral therapy","volume":"340","author":"Zhang","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.ymthe.2026.07.048_bib4","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 therapy","volume":"5","author":"Finzi","year":"1999","journal-title":"Nat. Med."},{"key":"10.1016\/j.ymthe.2026.07.048_bib5","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1038\/s41586-020-1951-3","article-title":"Systemic HIV and SIV latency reversal via non-canonical NF-kappaB signalling in vivo","volume":"578","author":"Nixon","year":"2020","journal-title":"Nature"},{"key":"10.1016\/j.ymthe.2026.07.048_bib6","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1038\/s41591-021-01590-5","article-title":"Research priorities for an HIV cure: International AIDS Society Global Scientific Strategy 2021","volume":"27","author":"Deeks","year":"2021","journal-title":"Nat. Med."},{"key":"10.1016\/j.ymthe.2026.07.048_bib7","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.idc.2024.06.001","article-title":"Advancing Toward a Human Immunodeficiency Virus Cure: Initial Progress on a Difficult Path","volume":"38","author":"Margolis","year":"2024","journal-title":"Infect Dis. Clin. North Am."},{"key":"10.1016\/j.ymthe.2026.07.048_bib8","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1038\/487439a","article-title":"HIV: Shock and kill","volume":"487","author":"Deeks","year":"2012","journal-title":"Nature"},{"key":"10.1016\/j.ymthe.2026.07.048_bib9","doi-asserted-by":"crossref","DOI":"10.1126\/science.aaf6517","article-title":"Latency reversal and viral clearance to cure HIV-1","volume":"353","author":"Margolis","year":"2016","journal-title":"Science"},{"key":"10.1016\/j.ymthe.2026.07.048_bib10","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1005142","article-title":"The Depsipeptide Romidepsin Reverses HIV-1 Latency In Vivo","volume":"11","author":"S\u00f8gaard","year":"2015","journal-title":"PLoS Pathog."},{"key":"10.1016\/j.ymthe.2026.07.048_bib11","doi-asserted-by":"crossref","first-page":"e13","DOI":"10.1016\/S2352-3018(14)70014-1","article-title":"Panobinostat, a histone deacetylase inhibitor, for latent-virus reactivation in HIV-infected patients on suppressive antiretroviral therapy: a phase 1\/2, single group, clinical trial","volume":"1","author":"Rasmussen","year":"2014","journal-title":"Lancet HIV"},{"key":"10.1016\/j.ymthe.2026.07.048_bib12","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1097\/QAD.0000000000001064","article-title":"Bryostatin-1 for latent virus reactivation in HIV-infected patients on antiretroviral therapy","volume":"30","author":"Guti\u00e9rrez","year":"2016","journal-title":"AIDS"},{"key":"10.1016\/j.ymthe.2026.07.048_bib13","doi-asserted-by":"crossref","first-page":"3126","DOI":"10.1172\/JCI92684","article-title":"Interval dosing with the HDAC inhibitor vorinostat effectively reverses HIV latency","volume":"127","author":"Archin","year":"2017","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.ymthe.2026.07.048_bib14","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1038\/nature11286","article-title":"Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy","volume":"487","author":"Archin","year":"2012","journal-title":"Nature"},{"key":"10.1016\/j.ymthe.2026.07.048_bib15","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1093\/cid\/cit813","article-title":"A pilot study assessing the safety and latency-reversing activity of disulfiram in HIV-1-infected adults on antiretroviral therapy","volume":"58","author":"Spivak","year":"2014","journal-title":"Clin. Infect. Dis."},{"key":"10.1016\/j.ymthe.2026.07.048_bib16","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1097\/QAD.0000000000002919","article-title":"The impact of immune checkpoint therapy on the latent reservoir in HIV-infected individuals with cancer on antiretroviral therapy","volume":"35","author":"Lau","year":"2021","journal-title":"AIDS"},{"key":"10.1016\/j.ymthe.2026.07.048_bib17","doi-asserted-by":"crossref","first-page":"e1973","DOI":"10.1093\/cid\/ciaa1530","article-title":"Impact of Anti-PD-1 and Anti-CTLA-4 on the Human Immunodeficiency Virus (HIV) Reservoir in People Living With HIV With Cancer on Antiretroviral Therapy: The AIDS Malignancy Consortium 095 Study","volume":"73","author":"Rasmussen","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"10.1016\/j.ymthe.2026.07.048_bib18","doi-asserted-by":"crossref","first-page":"823","DOI":"10.3389\/fimmu.2020.00823","article-title":"HIVconsv Vaccines and Romidepsin in Early-Treated HIV-1-Infected Individuals: Safety, Immunogenicity and Effect on the Viral Reservoir (Study BCN02)","volume":"11","author":"Mothe","year":"2020","journal-title":"Front. Immunol."},{"key":"10.1016\/j.ymthe.2026.07.048_bib19","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1016\/S0140-6736(19)32990-3","article-title":"Antiretroviral therapy alone versus antiretroviral therapy with a kick and kill approach, on measures of the HIV reservoir in participants with recent HIV infection (the RIVER trial): a phase 2, randomised trial","volume":"395","author":"Fidler","year":"2020","journal-title":"Lancet"},{"key":"10.1016\/j.ymthe.2026.07.048_bib20","doi-asserted-by":"crossref","first-page":"5134","DOI":"10.1038\/s41598-020-61878-3","article-title":"Assessing the impact of AGS-004, a dendritic cell-based immunotherapy, and vorinostat on persistent HIV-1 Infection","volume":"10","author":"Gay","year":"2020","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ymthe.2026.07.048_bib21","doi-asserted-by":"crossref","first-page":"2547","DOI":"10.1038\/s41591-023-02547-6","article-title":"Impact of a TLR9 agonist and broadly neutralizing antibodies on HIV-1 persistence: the randomized phase 2a TITAN trial","volume":"29","author":"Gunst","year":"2023","journal-title":"Nat. Med."},{"key":"10.1016\/j.ymthe.2026.07.048_bib22","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1093\/infdis\/jiab487","article-title":"Stable Latent HIV Infection and Low-level Viremia Despite Treatment With the Broadly Neutralizing Antibody VRC07-523LS and the Latency Reversal Agent Vorinostat","volume":"225","author":"Gay","year":"2022","journal-title":"J. Infect. Dis."},{"key":"10.1016\/j.ymthe.2026.07.048_bib23","doi-asserted-by":"crossref","first-page":"e203","DOI":"10.1016\/S2666-5247(21)00239-1","article-title":"Effect of 3BNC117 and romidepsin on the HIV-1 reservoir in people taking suppressive antiretroviral therapy (ROADMAP): a randomised, open-label, phase 2A trial","volume":"3","author":"Gruell","year":"2022","journal-title":"Lancet Microbe"},{"key":"10.1016\/j.ymthe.2026.07.048_bib24","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1016\/j.jhep.2014.07.004","article-title":"Hyper-IL-15 suppresses metastatic and autochthonous liver cancer by promoting tumour-specific CD8+ T cell responses","volume":"61","author":"Cheng","year":"2014","journal-title":"J. Hepatol."},{"key":"10.1016\/j.ymthe.2026.07.048_bib25","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1005545","article-title":"A Subset of Latency-Reversing Agents Expose HIV-Infected Resting CD4+ T-Cells to Recognition by Cytotoxic T-Lymphocytes","volume":"12","author":"Jones","year":"2016","journal-title":"PLoS Pathog."},{"key":"10.1016\/j.ymthe.2026.07.048_bib26","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-022-23010-5","article-title":"Impact of IL-15 and latency reversing agent combinations in the reactivation and NK cell-mediated suppression of the HIV reservoir","volume":"12","author":"Covino","year":"2022","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ymthe.2026.07.048_bib27","doi-asserted-by":"crossref","first-page":"3075","DOI":"10.1158\/0008-5472.CAN-12-2357","article-title":"Efficacy and mechanism-of-action of a novel superagonist interleukin-15: interleukin-15 receptor alphaSu\/Fc fusion complex in syngeneic murine models of multiple myeloma","volume":"73","author":"Xu","year":"2013","journal-title":"Cancer Res."},{"key":"10.1016\/j.ymthe.2026.07.048_bib28","doi-asserted-by":"crossref","first-page":"6264","DOI":"10.1128\/JVI.00563-15","article-title":"In Vivo Activation of Human NK Cells by Treatment with an Interleukin-15 Superagonist Potently Inhibits Acute In Vivo HIV-1 Infection in Humanized Mice","volume":"89","author":"Seay","year":"2015","journal-title":"J. Virol."},{"key":"10.1016\/j.ymthe.2026.07.048_bib29","doi-asserted-by":"crossref","DOI":"10.1128\/JVI.00235-18","article-title":"Interleukin-15-Stimulated Natural Killer Cells Clear HIV-1-Infected Cells following Latency Reversal Ex Vivo","volume":"92","author":"Garrido","year":"2018","journal-title":"J. Virol."},{"key":"10.1016\/j.ymthe.2026.07.048_bib30","doi-asserted-by":"crossref","DOI":"10.1128\/JVI.01748-17","article-title":"ALT-803 Transiently Reduces Simian Immunodeficiency Virus Replication in the Absence of Antiretroviral Treatment","volume":"92","author":"Ellis-Connell","year":"2018","journal-title":"J. Virol."},{"key":"10.1016\/j.ymthe.2026.07.048_bib31","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1008339","article-title":"The human IL-15 superagonist N-803 promotes migration of virus-specific CD8+ T and NK cells to B cell follicles but does not reverse latency in ART-suppressed, SHIV-infected macaques","volume":"16","author":"Webb","year":"2020","journal-title":"PLoS Pathog."},{"key":"10.1016\/j.ymthe.2026.07.048_bib32","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":"10.1016\/j.ymthe.2026.07.048_bib33","doi-asserted-by":"crossref","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":"10.1016\/j.ymthe.2026.07.048_bib34","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1182\/bloodadvances.2017012971","article-title":"The human IL-15 superagonist ALT-803 directs SIV-specific CD8(+) T cells into B-cell follicles","volume":"2","author":"Webb","year":"2018","journal-title":"Blood Adv."},{"key":"10.1016\/j.ymthe.2026.07.048_bib35","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":"10.1016\/j.ymthe.2026.07.048_bib36","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/0092-8674(86)90590-8","article-title":"The T4 gene encodes the AIDS virus receptor and is expressed in the immune system and the brain","volume":"47","author":"Maddon","year":"1986","journal-title":"Cell"},{"key":"10.1016\/j.ymthe.2026.07.048_bib37","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1126\/science.3001934","article-title":"Binding of HTLV-III\/LAV to T4+ T cells by a complex of the 110K viral protein and the T4 molecule","volume":"231","author":"McDougal","year":"1986","journal-title":"Science"},{"key":"10.1016\/j.ymthe.2026.07.048_bib38","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.1126\/science.3500514","article-title":"Blocking of HIV-1 infectivity by a soluble, secreted form of the CD4 antigen","volume":"238","author":"Smith","year":"1987","journal-title":"Science"},{"key":"10.1016\/j.ymthe.2026.07.048_bib39","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1016\/j.chom.2021.04.014","article-title":"Modulating HIV-1 envelope glycoprotein conformation to decrease the HIV-1 reservoir","volume":"29","author":"Rajashekar","year":"2021","journal-title":"Cell Host Microbe"},{"key":"10.1016\/j.ymthe.2026.07.048_bib40","doi-asserted-by":"crossref","first-page":"E2687","DOI":"10.1073\/pnas.1506755112","article-title":"CD4 mimetics sensitize HIV-1-infected cells to ADCC","volume":"112","author":"Richard","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ymthe.2026.07.048_bib41","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1016\/j.cell.2014.08.023","article-title":"Broadly neutralizing anti-HIV-1 antibodies require Fc effector functions for in vivo activity","volume":"158","author":"Bournazos","year":"2014","journal-title":"Cell"},{"key":"10.1016\/j.ymthe.2026.07.048_bib42","doi-asserted-by":"crossref","DOI":"10.4161\/21624011.2014.963409","article-title":"Immunotherapy of metastatic and autochthonous liver cancer with IL-15\/IL-15Ralpha fusion protein","volume":"3","author":"Cheng","year":"2014","journal-title":"Oncoimmunology"},{"key":"10.1016\/j.ymthe.2026.07.048_bib43","doi-asserted-by":"crossref","first-page":"7972","DOI":"10.1128\/JVI.73.10.7972-7980.1999","article-title":"CD40-Mediated Induction of CD4 and CXCR4 on B Lymphocytes Correlates with Restricted Susceptibility to Human Immunodeficiency Virus Type 1 Infection: Potential Role of B Lymphocytes as a Viral Reservoir","volume":"73","author":"Moir","year":"1999","journal-title":"J. Virol."},{"key":"10.1016\/j.ymthe.2026.07.048_bib44","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1128\/JVI.02868-14","article-title":"The HIV-1 gp120 CD4-bound conformation is preferentially targeted by antibody-dependent cellular cytotoxicity-mediating antibodies in sera from HIV-1-infected individuals","volume":"89","author":"Veillette","year":"2015","journal-title":"J. Virol."},{"key":"10.1016\/j.ymthe.2026.07.048_bib45","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.3390\/v12111279","article-title":"Experimental Systems for Measuring HIV Latency and Reactivation","volume":"12","author":"Fujinaga","year":"2020","journal-title":"Viruses"},{"key":"10.1016\/j.ymthe.2026.07.048_bib46","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1038\/s41467-017-00515-6","article-title":"Envelope glycoprotein mobility on HIV-1 particles depends on the virus maturation state","volume":"8","author":"Chojnacki","year":"2017","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ymthe.2026.07.048_bib47","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1126\/science.1226359","article-title":"Maturation-dependent HIV-1 surface protein redistribution revealed by fluorescence nanoscopy","volume":"338","author":"Chojnacki","year":"2012","journal-title":"Science"},{"key":"10.1016\/j.ymthe.2026.07.048_bib48","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1038\/328626a0","article-title":"Functional interaction between human T-cell protein CD4 and the major histocompatibility complex HLA-DR antigen","volume":"328","author":"Gay","year":"1987","journal-title":"Nature"},{"key":"10.1016\/j.ymthe.2026.07.048_bib49","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/0092-8674(88)90397-2","article-title":"The CD4 antigen: physiological ligand and HIV receptor","volume":"52","author":"Sattentau","year":"1988","journal-title":"Cell"},{"key":"10.1016\/j.ymthe.2026.07.048_bib50","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/0092-8674(88)90036-0","article-title":"Immunosuppressive properties of synthetic peptides derived from CD4 and HLA-DR antigens","volume":"55","author":"Mazerolles","year":"1988","journal-title":"Cell"},{"key":"10.1016\/j.ymthe.2026.07.048_bib51","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1093\/protein\/gzw040","article-title":"Novel human IgG1 and IgG4 Fc-engineered antibodies with completely abolished immune effector functions","volume":"29","author":"Schlothauer","year":"2016","journal-title":"Protein Eng. Des. Sel."},{"key":"10.1016\/j.ymthe.2026.07.048_bib52","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1038\/nm.4347","article-title":"Novel assay reveals a large, inducible, replication-competent HIV-1 reservoir in resting CD4(+) T cells","volume":"23","author":"Sanyal","year":"2017","journal-title":"Nat. Med."},{"key":"10.1016\/j.ymthe.2026.07.048_bib53","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1097\/00042560-199510020-00006","article-title":"Safety, pharmacokinetics, and antiviral response of CD4-immunoglobulin G by intravenous bolus in AIDS and AIDS-related complex","volume":"10","author":"Collier","year":"1995","journal-title":"J. Acquir. Immune Defic. Syndr. Hum. Retrovirol."},{"key":"10.1016\/j.ymthe.2026.07.048_bib54","doi-asserted-by":"crossref","first-page":"2580","DOI":"10.1128\/AAC.35.12.2580","article-title":"Phase 1 study of recombinant human CD4-immunoglobulin G therapy of patients with AIDS and AIDS-related complex","volume":"35","author":"Hodges","year":"1991","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.ymthe.2026.07.048_bib55","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1086\/315698","article-title":"Single-dose safety, pharmacology, and antiviral activity of the human immunodeficiency virus (HIV) type 1 entry inhibitor PRO 542 in HIV-infected adults","volume":"182","author":"Jacobson","year":"2000","journal-title":"J. Infect Dis."},{"key":"10.1016\/j.ymthe.2026.07.048_bib56","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1172\/JCI90745","article-title":"Blocking type I interferon signaling enhances T cell recovery and reduces HIV-1 reservoirs","volume":"127","author":"Cheng","year":"2016","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.ymthe.2026.07.048_bib57","doi-asserted-by":"crossref","first-page":"4387","DOI":"10.1172\/JCI99005","article-title":"TLR3 agonist and CD40-targeting vaccination induces immune responses and reduces HIV-1 reservoirs","volume":"128","author":"Cheng","year":"2018","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.ymthe.2026.07.048_bib58","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.celrep.2014.02.041","article-title":"A humanized mouse identifies the bone marrow as a niche with low therapeutic IgG activity","volume":"7","author":"Lux","year":"2014","journal-title":"Cell Rep."},{"key":"10.1016\/j.ymthe.2026.07.048_bib59","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1016\/j.cell.2013.12.041","article-title":"Sensitizing protective tumor microenvironments to antibody-mediated therapy","volume":"156","author":"Pallasch","year":"2014","journal-title":"Cell"},{"key":"10.1016\/j.ymthe.2026.07.048_bib60","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1126\/science.adf7966","article-title":"Induction of durable remission by dual immunotherapy in SHIV-infected ART-suppressed macaques","volume":"383","author":"Lim","year":"2024","journal-title":"Science"},{"key":"10.1016\/j.ymthe.2026.07.048_bib61","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":"10.1016\/j.ymthe.2026.07.048_bib62","doi-asserted-by":"crossref","DOI":"10.1016\/j.smim.2020.101412","article-title":"Immunological approaches to HIV cure","volume":"51","author":"Ward","year":"2021","journal-title":"Semin. Immunol."},{"key":"10.1016\/j.ymthe.2026.07.048_bib63","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1016\/S0140-6736(20)30264-6","article-title":"Kick and kill for HIV latency","volume":"395","author":"Lewin","year":"2020","journal-title":"The Lancet"},{"key":"10.1016\/j.ymthe.2026.07.048_bib64","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.cell.2020.03.005","article-title":"Curing HIV: Seeking to Target and Clear Persistent Infection","volume":"181","author":"Margolis","year":"2020","journal-title":"Cell"},{"key":"10.1016\/j.ymthe.2026.07.048_bib65","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.190831","article-title":"Impact of the IL-15 superagonist N-803 on lymphatic reservoirs of HIV","volume":"10","author":"Rhein","year":"2025","journal-title":"JCI Insight"},{"key":"10.1016\/j.ymthe.2026.07.048_bib66","doi-asserted-by":"crossref","first-page":"2535","DOI":"10.1038\/s41591-023-02570-7","article-title":"AZD5582 plus SIV-specific antibodies reduce lymph node viral reservoirs in antiretroviral therapy-suppressed macaques","volume":"29","author":"Dashti","year":"2023","journal-title":"Nat. Med."},{"key":"10.1016\/j.ymthe.2026.07.048_bib67","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1038\/s41590-023-01741-5","article-title":"Bispecific antibodies promote natural killer cell-mediated elimination of HIV-1 reservoir cells","volume":"25","author":"Board","year":"2024","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.ymthe.2026.07.048_bib68","article-title":"Bispecific antibody-derived molecules to target persistent HIV infection","volume":"8","author":"Nordstrom","year":"2022","journal-title":"J. Virus Erad."},{"key":"10.1016\/j.ymthe.2026.07.048_bib69","doi-asserted-by":"crossref","first-page":"9130","DOI":"10.1038\/s41598-017-07966-3","article-title":"One-domain CD4 fused to human anti-CD16 antibody domain mediates effective killing of HIV-1-infected cells","volume":"7","author":"Li","year":"2017","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ymthe.2026.07.048_bib70","doi-asserted-by":"crossref","first-page":"2517","DOI":"10.1182\/blood.V128.22.2517.2517","article-title":"A novel HIV envelope Bi-specific killer engager enhances natural killer cell mediated ADCC responses against HIV-infected cells","volume":"128","author":"Davis","year":"2016","journal-title":"Blood"},{"key":"10.1016\/j.ymthe.2026.07.048_bib71","doi-asserted-by":"crossref","first-page":"4077","DOI":"10.1172\/JCI82314","article-title":"Dual-Affinity Re-Targeting proteins direct T cell-mediated cytolysis of latently HIV-infected cells","volume":"125","author":"Sung","year":"2015","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.ymthe.2026.07.048_bib72","doi-asserted-by":"crossref","first-page":"8447","DOI":"10.1038\/ncomms9447","article-title":"Activation and lysis of human CD4 cells latently infected with HIV-1","volume":"6","author":"Pegu","year":"2015","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ymthe.2026.07.048_bib73","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1005233","article-title":"Targeting HIV Reservoir in Infected CD4 T Cells by Dual-Affinity Re-targeting Molecules (DARTs) that Bind HIV Envelope and Recruit Cytotoxic T Cells","volume":"11","author":"Sloan","year":"2015","journal-title":"PLoS Pathog."},{"key":"10.1016\/j.ymthe.2026.07.048_bib74","doi-asserted-by":"crossref","first-page":"713","DOI":"10.3389\/fimmu.2020.00713","article-title":"Redirection of Cord Blood T Cells and Natural Killer Cells for Elimination of Autologous HIV-1-Infected Target Cells Using Bispecific DART(R) Molecules","volume":"11","author":"Pollara","year":"2020","journal-title":"Front. Immunol."},{"key":"10.1016\/j.ymthe.2026.07.048_bib75","doi-asserted-by":"crossref","DOI":"10.1128\/JVI.00793-20","article-title":"SMAC mimetic plus triple-combination bispecific HIVxCD3 retargeting molecules in SHIV. C. CH505-infected, antiretroviral therapy-suppressed rhesus macaques","volume":"94","author":"Dashti","year":"2020","journal-title":"J. Virol."},{"key":"10.1016\/j.ymthe.2026.07.048_bib76","doi-asserted-by":"crossref","first-page":"3719","DOI":"10.1038\/s41467-023-39265-z","article-title":"Trispecific antibody targeting HIV-1 and T cells activates and eliminates latently-infected cells in HIV\/SHIV infections","volume":"14","author":"Promsote","year":"2023","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ymthe.2026.07.048_bib77","doi-asserted-by":"crossref","DOI":"10.1080\/2162402X.2022.2083479","article-title":"Novel strategies for the mitigation of cytokine release syndrome induced by T cell engaging therapies with a focus on the use of kinase inhibitors","volume":"11","author":"Leclercq","year":"2022","journal-title":"Oncoimmunology"},{"key":"10.1016\/j.ymthe.2026.07.048_bib78","doi-asserted-by":"crossref","first-page":"2515","DOI":"10.1182\/blood-2017-12-823757","article-title":"First-in-human phase 1 clinical study of the IL-15 superagonist complex ALT-803 to treat relapse after transplantation","volume":"131","author":"Romee","year":"2018","journal-title":"Blood"},{"key":"10.1016\/j.ymthe.2026.07.048_bib79","doi-asserted-by":"crossref","first-page":"6444","DOI":"10.1073\/pnas.92.14.6444","article-title":"Oligomerization of CD4 is required for stable binding to class II major histocompatibility complex proteins but not for interaction with human immunodeficiency virus gp120","volume":"92","author":"Sakihama","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ymthe.2026.07.048_bib80","doi-asserted-by":"crossref","first-page":"29870","DOI":"10.1021\/acsomega.4c03796","article-title":"Integrated ML-based strategy identifies drug repurposing for idiopathic pulmonary fibrosis","volume":"9","author":"Ahmed","year":"2024","journal-title":"ACS omega"},{"key":"10.1016\/j.ymthe.2026.07.048_bib81","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.trsl.2023.07.010","article-title":"Artificial intelligence-assisted repurposing of lubiprostone alleviates tubulointerstitial fibrosis","volume":"262","author":"Samantasinghar","year":"2023","journal-title":"Translational Res."},{"key":"10.1016\/j.ymthe.2026.07.048_bib82","doi-asserted-by":"crossref","DOI":"10.1002\/jmv.28693","article-title":"Drug repurposing for viral cancers: A paradigm of machine learning, deep learning, and virtual screening-based approaches","volume":"95","author":"Ahmed","year":"2023","journal-title":"J. Med. Virol."},{"key":"10.1016\/j.ymthe.2026.07.048_bib83","doi-asserted-by":"crossref","first-page":"5186","DOI":"10.1016\/j.csbj.2023.10.038","article-title":"Network-based drug repurposing for HPV-associated cervical cancer","volume":"21","author":"Ahmed","year":"2023","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"10.1016\/j.ymthe.2026.07.048_bib84","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1038\/nri3311","article-title":"Humanized mice for immune system investigation: progress, promise and challenges","volume":"12","author":"Shultz","year":"2012","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.ymthe.2026.07.048_bib85","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0044664","article-title":"Graft versus host disease in the bone marrow, liver and thymus humanized mouse model","volume":"7","author":"Greenblatt","year":"2012","journal-title":"PLoS One"},{"key":"10.1016\/j.ymthe.2026.07.048_bib86","doi-asserted-by":"crossref","first-page":"817","DOI":"10.3389\/fimmu.2018.00817","article-title":"Humanized Mice Engrafted With Human HSC Only or HSC and Thymus Support Comparable HIV-1 Replication, Immunopathology, and Responses to ART and Immune Therapy","volume":"9","author":"Cheng","year":"2018","journal-title":"Front. Immunol."},{"key":"10.1016\/j.ymthe.2026.07.048_bib87","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1208\/s12248-022-00739-5","article-title":"Determinants of biological half-lives and terminal slopes in physiologically based pharmacokinetic systems: assessment of limiting conditions","volume":"24","author":"Jeong","year":"2022","journal-title":"AAPS J."},{"key":"10.1016\/j.ymthe.2026.07.048_bib88","series-title":"HIV Protocols","first-page":"239","article-title":"Measuring the Frequency of Latent HIV-1 in Resting CD4+ T Cells Using a Limiting Dilution Coculture Assay","author":"Laird","year":"2016"}],"container-title":["Molecular Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525001626006696?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525001626006696?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T15:33:47Z","timestamp":1793374427000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1525001626006696"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":88,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["S1525001626006696"],"URL":"https:\/\/doi.org\/10.1016\/j.ymthe.2026.07.048","relation":{},"ISSN":["1525-0016"],"issn-type":[{"value":"1525-0016","type":"print"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Synchronized latency reversal and immune clearance by a multifunctional fusion protein enables HIV-1 reservoir reduction","name":"articletitle","label":"Article Title"},{"value":"Molecular Therapy","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ymthe.2026.07.048","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}]}}