{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T11:53:49Z","timestamp":1790855629841,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1009831","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,2,17]],"date-time":"2022-02-17T00:00:00Z","timestamp":1645056000000}}],"reference-count":109,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2022,2,7]],"date-time":"2022-02-07T00:00:00Z","timestamp":1644192000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"national institutes of health","doi-asserted-by":"publisher","award":["5R01AI096966-06S1"],"award-info":[{"award-number":["5R01AI096966-06S1"]}],"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":["1UM1AI26617"],"award-info":[{"award-number":["1UM1AI26617"]}],"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":["P51OD011106\/P51RR000167"],"award-info":[{"award-number":["P51OD011106\/P51RR000167"]}],"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":["5U01HL127479-03"],"award-info":[{"award-number":["5U01HL127479-03"]}],"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":["R01AI143380"],"award-info":[{"award-number":["R01AI143380"]}],"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":["1UM14126617"],"award-info":[{"award-number":["1UM14126617"]}],"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":["5-T32 AI 55433"],"award-info":[{"award-number":["5-T32 AI 55433"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006492","name":"division of intramural research, national institute of allergy and infectious diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["Intramural AIDS Targeted Antiviral Program"],"award-info":[{"award-number":["Intramural AIDS Targeted Antiviral Program"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    During chronic human immunodeficiency virus (HIV) or simian immunodeficiency virus (SIV) infection prior to AIDS progression, the vast majority of viral replication is concentrated within B cell follicles of secondary lymphoid tissues. We investigated whether infusion of T cells expressing an SIV-specific chimeric antigen receptor (CAR) and the follicular homing receptor, CXCR5, could successfully kill viral-RNA\n                    <jats:sup>+<\/jats:sup>\n                    cells in targeted lymphoid follicles in SIV-infected rhesus macaques. In this study, CD4 and CD8 T cells from rhesus macaques were genetically modified to express antiviral CAR and CXCR5 moieties (generating CAR\/CXCR5-T cells) and autologously infused into a chronically infected animal. At 2 days post-treatment, the CAR\/CXCR5-T cells were located primarily in spleen and lymph nodes both inside and outside of lymphoid follicles. Few CAR\/CXCR5-T cells were detected in the ileum, rectum, and lung, and no cells were detected in the bone marrow, liver, or brain. Within follicles, CAR\/CXCR5-T cells were found in direct contact with SIV-viral RNA\n                    <jats:sup>+<\/jats:sup>\n                    cells. We next infused CAR\/CXCR5-T cells into ART-suppressed SIV-infected rhesus macaques, in which the animals were released from ART at the time of infusion. These CAR\/CXCR5-T cells replicated in vivo within both the extrafollicular and follicular regions of lymph nodes and accumulated within lymphoid follicles. CAR\/CXR5-T cell concentrations in follicles peaked during the first week post-infusion but declined to undetectable levels after 2 to 4 weeks. Overall, CAR\/CXCR5-T cell-treated animals maintained lower viral loads and follicular viral RNA levels than untreated control animals, and no outstanding adverse reactions were noted. These findings indicate that CAR\/CXCR5-T cell treatment is safe and holds promise as a future treatment for the durable remission of HIV.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1009831","type":"journal-article","created":{"date-parts":[[2022,2,7]],"date-time":"2022-02-07T13:33:03Z","timestamp":1644240783000},"page":"e1009831","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":47,"title":["CAR\/CXCR5-T cell immunotherapy is safe and potentially efficacious in promoting sustained remission of SIV infection"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6973-9474","authenticated-orcid":true,"given":"Mary S.","family":"Pampusch","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadia M.","family":"Abdelaal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily K.","family":"Cartwright","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6244-0827","authenticated-orcid":true,"given":"Jhomary S.","family":"Molden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5154-9077","authenticated-orcid":true,"given":"Brianna C.","family":"Davey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan D.","family":"Sauve","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily N.","family":"Sevcik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5434-3592","authenticated-orcid":true,"given":"Aaron K.","family":"Rendahl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8197-5309","authenticated-orcid":true,"given":"Eva G.","family":"Rakasz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0465-6248","authenticated-orcid":true,"given":"Elizabeth","family":"Connick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward A.","family":"Berger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3388-1687","authenticated-orcid":true,"given":"Pamela J.","family":"Skinner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,2,7]]},"reference":[{"key":"ppat.1009831.ref001","unstructured":"HIV\/AIDS. [cited 3 Nov 2021]. Available: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/hiv-aids."},{"key":"ppat.1009831.ref002","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":"L Zhang","year":"1999","journal-title":"N Engl J Med"},{"key":"ppat.1009831.ref003","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1126\/science.278.5341.1291","article-title":"Recovery of replication-competent HIV despite prolonged suppression of plasma viremia","volume":"278","author":"JK Wong","year":"1997","journal-title":"Science"},{"key":"ppat.1009831.ref004","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1006\/mthe.2002.0611","article-title":"A phase II randomized study of HIV-specific T-cell gene therapy in subjects with undetectable plasma viremia on combination antiretroviral therapy","volume":"5","author":"SG Deeks","year":"2002","journal-title":"Mol Ther"},{"key":"ppat.1009831.ref005","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1517\/14740338.2013.806480","article-title":"Antiretroviral drug-related toxicities\u2014clinical spectrum, prevention, and management.","volume":"12","author":"JV Fernandez-Montero","year":"2013","journal-title":"Expert Opin Drug Saf"},{"key":"ppat.1009831.ref006","doi-asserted-by":"crossref","first-page":"831","DOI":"10.3389\/fphar.2017.00831","article-title":"Improving the Adherence to Antiretroviral Therapy, a Difficult but Essential Task for a Successful HIV Treatment\u2014Clinical Points of View and Practical Considerations.","volume":"8","author":"SA Iacob","year":"2017","journal-title":"Front Pharmacol"},{"key":"ppat.1009831.ref007","volume-title":"Monitoring Selected National HIV Prevention and Care Objectives by Using HIV Surveillance Data.","author":"Centers for Disease Control and Prevention","year":"2018"},{"key":"ppat.1009831.ref008","first-page":"229","article-title":"Adverse effects of antiretroviral therapy for HIV infection.","volume":"170","author":"V Montessori","year":"2004","journal-title":"CMAJ"},{"key":"ppat.1009831.ref009","first-page":"1443","article-title":"Common adverse effects of antiretroviral therapy for HIV disease","volume":"83","author":"CE Reust","year":"2011","journal-title":"Am Fam Physician"},{"key":"ppat.1009831.ref010","unstructured":"HIV\/AIDS. HIV drug resistance report 2019. World Health Organization; 1 Jul 2019 [cited 3 Nov 2021]. Available: https:\/\/www.who.int\/publications\/i\/item\/WHO-CDS-HIV-19.21."},{"key":"ppat.1009831.ref011","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/s41586-019-1841-8","article-title":"Why and where an HIV cure is needed and how it might be achieved","volume":"576","author":"T Ndung\u2019u","year":"2019","journal-title":"Nature"},{"key":"ppat.1009831.ref012","doi-asserted-by":"crossref","first-page":"6685","DOI":"10.1128\/JVI.00474-15","article-title":"Novel CD4-Based Bispecific Chimeric Antigen Receptor Designed for Enhanced Anti-HIV Potency and Absence of HIV Entry Receptor Activity","volume":"89","author":"L Liu","year":"2015","journal-title":"J Virol"},{"key":"ppat.1009831.ref013","doi-asserted-by":"crossref","first-page":"2109","DOI":"10.1016\/S0140-6736(13)60104-X","article-title":"Barriers to a cure for HIV: new ways to target and eradicate HIV-1 reservoirs","volume":"381","author":"C Katlama","year":"2013","journal-title":"Lancet"},{"key":"ppat.1009831.ref014","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.jaci.2014.05.026","article-title":"Recent developments in the search for a cure for HIV-1 infection: targeting the latent reservoir for HIV-1","volume":"134","author":"JD Siliciano","year":"2014","journal-title":"J Allergy Clin Immunol"},{"key":"ppat.1009831.ref015","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/S0140-6736(14)61181-8","article-title":"Towards a cure for HIV\u2014are we making progress?","volume":"384","author":"SR Lewin","year":"2014","journal-title":"Lancet"},{"key":"ppat.1009831.ref016","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1097\/QCO.0000000000000026","article-title":"Emerging strategies to deplete the HIV reservoir.","volume":"27","author":"NM Archin","year":"2014","journal-title":"Curr Opin Infect Dis"},{"key":"ppat.1009831.ref017","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S2055-6640(20)31152-3","article-title":"HIV cure research: a formidable challenge","author":"J Ananworanich","year":"2015","journal-title":"Journal of Virus Eradication"},{"key":"ppat.1009831.ref018","doi-asserted-by":"crossref","first-page":"2531","DOI":"10.1056\/NEJMoa1707447","article-title":"Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma","volume":"377","author":"SS Neelapu","year":"2017","journal-title":"N Engl J Med"},{"key":"ppat.1009831.ref019","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1056\/NEJMoa1709866","article-title":"Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia","volume":"378","author":"SL Maude","year":"2018","journal-title":"N Engl J Med"},{"key":"ppat.1009831.ref020","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1056\/NEJMoa1804980","article-title":"Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma","volume":"380","author":"SJ Schuster","year":"2019","journal-title":"N Engl J Med"},{"key":"ppat.1009831.ref021","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1093\/bfgp\/elz042","article-title":"Applications and explorations of CRISPR\/Cas9 in CAR T-cell therapy.","author":"C Li","year":"2020","journal-title":"Briefings in Functional Genomics"},{"key":"ppat.1009831.ref022","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/s41573-019-0051-2","article-title":"\u201cOff-the-shelf\u201d allogeneic CAR T cells: development and challenges.","volume":"19","author":"S Depil","year":"2020","journal-title":"Nat Rev Drug Discov"},{"key":"ppat.1009831.ref023","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.jcyt.2017.11.001","article-title":"Bispecific chimeric antigen receptors targeting the CD4 binding site and high-mannose Glycans of gp120 optimized for anti\u2013human immunodeficiency virus potency and breadth with minimal immunogenicity.","volume":"20","author":"MH Ghanem","year":"2018","journal-title":"Cytotherapy"},{"key":"ppat.1009831.ref024","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1089\/aid.2005.21.363","article-title":"Lymphoid follicles are sites of heightened human immunodeficiency virus type 1 (HIV-1) replication and reduced antiretroviral effector mechanisms.","volume":"21","author":"JM Folkvord","year":"2005","journal-title":"AIDS Res Hum Retroviruses"},{"key":"ppat.1009831.ref025","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1097\/00002030-199707000-00003","article-title":"Germinal centre CD4+ T cells are an important site of HIV replication in vivo","volume":"11","author":"FT Hufert","year":"1997","journal-title":"AIDS"},{"key":"ppat.1009831.ref026","doi-asserted-by":"crossref","first-page":"6975","DOI":"10.4049\/jimmunol.178.11.6975","article-title":"CTL Fail to Accumulate at Sites of HIV-1 Replication in Lymphoid Tissue","author":"E Connick","year":"2007","journal-title":"The Journal of Immunology"},{"key":"ppat.1009831.ref027","doi-asserted-by":"crossref","first-page":"5613","DOI":"10.4049\/jimmunol.1401161","article-title":"Compartmentalization of simian immunodeficiency virus replication within secondary lymphoid tissues of rhesus macaques is linked to disease stage and inversely related to localization of virus-specific CTL","volume":"193","author":"E Connick","year":"2014","journal-title":"J Immunol"},{"key":"ppat.1009831.ref028","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1084\/jem.187.6.949","article-title":"The unenlarged lymph nodes of HIV-1\u2014infected, asymptomatic patients with high CD4 T cell counts are sites for virus replication and CD4 T cell proliferation. The impact of highly active antiretroviral therapy","volume":"187","author":"K Tenner-Racz","year":"1998","journal-title":"J Exp Med"},{"key":"ppat.1009831.ref029","first-page":"436","article-title":"HTLV-III expression in infected lymph nodes and relevance to pathogenesis of lymphadenopathy","volume":"125","author":"P Biberfeld","year":"1986","journal-title":"Am J Pathol"},{"key":"ppat.1009831.ref030","doi-asserted-by":"crossref","first-page":"4172","DOI":"10.1182\/blood-2012-06-437608","article-title":"Differential infection patterns of CD4+ T cells and lymphoid tissue viral burden distinguish progressive and nonprogressive lentiviral infections","volume":"120","author":"JM Brenchley","year":"2012","journal-title":"Blood"},{"key":"ppat.1009831.ref031","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1084\/jem.20121932","article-title":"Follicular helper T cells serve as the major CD4 T cell compartment for HIV-1 infection, replication, and production","volume":"210","author":"M Perreau","year":"2013","journal-title":"J Exp Med"},{"key":"ppat.1009831.ref032","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1038\/nm.3781","article-title":"B cell follicle sanctuary permits persistent productive simian immunodeficiency virus infection in elite controllers","volume":"21","author":"Y Fukazawa","year":"2015","journal-title":"Nat Med"},{"key":"ppat.1009831.ref033","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1038\/nm0703-847","article-title":"Transmission, acute HIV-1 infection and the quest for strategies to prevent infection","volume":"9","author":"M Pope","year":"2003","journal-title":"Nat Med"},{"key":"ppat.1009831.ref034","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1038\/362355a0","article-title":"HIV infection is active and progressive in lymphoid tissue during the clinically latent stage of disease","volume":"362","author":"G Pantaleo","year":"1993","journal-title":"Nature"},{"key":"ppat.1009831.ref035","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/362359a0","article-title":"Massive covert infection of helper T lymphocytes and macrophages by HIV during the incubation period of AIDS","volume":"362","author":"J Embretson","year":"1993","journal-title":"Nature"},{"key":"ppat.1009831.ref036","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1086\/315178","article-title":"Rapid Accumulation of Human Immunodeficiency Virus (HIV) in Lymphatic Tissue Reservoirs During Acute and Early HIV Infection: Implications for Timing of Antiretroviral Therapy.","volume":"181","author":"T Schacker","year":"2000","journal-title":"J Infect Dis"},{"key":"ppat.1009831.ref037","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1126\/science.274.5289.985","article-title":"Quantitative image analysis of HIV-1 infection in lymphoid tissue","volume":"274","author":"AT Haase","year":"1996","journal-title":"Science"},{"key":"ppat.1009831.ref038","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1093\/infdis\/164.6.1051","article-title":"Lymphoid germinal centers are reservoirs of human immunodeficiency virus type 1 RNA","volume":"164","author":"CH Fox","year":"1991","journal-title":"J Infect Dis"},{"key":"ppat.1009831.ref039","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1038\/377740a0","article-title":"Follicular dendritic cells and human immunodeficiency virus infectivity","volume":"377","author":"SL Heath","year":"1995","journal-title":"Nature"},{"key":"ppat.1009831.ref040","doi-asserted-by":"crossref","first-page":"2408","DOI":"10.4049\/jimmunol.168.5.2408","article-title":"Follicular Dendritic Cells and the Persistence of HIV Infectivity: The Role of Antibodies and Fc\u03b3 Receptors","volume":"168","author":"BA Smith-Franklin","year":"2002","journal-title":"The Journal of Immunology"},{"key":"ppat.1009831.ref041","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.4049\/jimmunol.150.3.1065","article-title":"Binding of human immunodeficiency virus type-1 to follicular dendritic cells in vitro is complement dependent","volume":"150","author":"P Joling","year":"1993","journal-title":"J Immunol"},{"key":"ppat.1009831.ref042","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/1742-4690-7-12","article-title":"In situ detection of Gag-specific CD8+ cells in the GI tract of SIV infected Rhesus macaques.","volume":"7","author":"A Tjernlund","year":"2010","journal-title":"Retrovirology"},{"key":"ppat.1009831.ref043","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0081623","article-title":"Location and dynamics of the immunodominant CD8 T cell response to SIV\u0394nef immunization and SIVmac251 vaginal challenge.","volume":"8","author":"AK Sasikala-Appukuttan","year":"2013","journal-title":"PLoS One"},{"key":"ppat.1009831.ref044","doi-asserted-by":"crossref","first-page":"e1007311","DOI":"10.1371\/journal.ppat.1007311","article-title":"Low levels of SIV-specific CD8+ T cells in germinal centers characterizes acute SIV infection.","volume":"15","author":"S Li","year":"2019","journal-title":"PLoS Pathog"},{"key":"ppat.1009831.ref045","doi-asserted-by":"crossref","first-page":"1726","DOI":"10.1126\/science.1168676","article-title":"Visualizing antigen-specific and infected cells in situ predicts outcomes in early viral infection","volume":"323","author":"Q Li","year":"2009","journal-title":"Science"},{"key":"ppat.1009831.ref046","article-title":"Simian immunodeficiency virus-producing cells in follicles are partially suppressed by CD8+ cells in vivo","volume":"90","author":"S Li","year":"2016","journal-title":"J Virol"},{"key":"ppat.1009831.ref047","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1016\/S0092-8674(00)81798-5","article-title":"A putative chemokine receptor, BLR1, directs B cell migration to defined lymphoid organs and specific anatomic compartments of the spleen","volume":"87","author":"R F\u00f6rster","year":"1996","journal-title":"Cell"},{"key":"ppat.1009831.ref048","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1084\/jem.192.11.1553","article-title":"CXC chemokine receptor 5 expression defines follicular homing T cells with B cell helper function","volume":"192","author":"P Schaerli","year":"2000","journal-title":"J Exp Med"},{"key":"ppat.1009831.ref049","doi-asserted-by":"crossref","first-page":"5099","DOI":"10.4049\/jimmunol.179.8.5099","article-title":"Role of CXCR5 and CCR7 in follicular Th cell positioning and appearance of a programmed cell death gene-1high germinal center-associated subpopulation","volume":"179","author":"NM Haynes","year":"2007","journal-title":"J Immunol"},{"key":"ppat.1009831.ref050","doi-asserted-by":"crossref","first-page":"3352","DOI":"10.1002\/eji.200636746","article-title":"CXCR5+ CCR7\u2013 CD8 T cells are early effector memory cells that infiltrate tonsil B cell follicles","volume":"37","author":"MF Quigley","year":"2007","journal-title":"Eur. J. Immunol."},{"key":"ppat.1009831.ref051","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1038\/35876","article-title":"A B-cell-homing chemokine made in lymphoid follicles activates Burkitt\u2019s lymphoma receptor-1","volume":"391","author":"MD Gunn","year":"1998","journal-title":"Nature"},{"key":"ppat.1009831.ref052","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1084\/jem.187.4.655","article-title":"B cell-attracting chemokine 1, a human CXC chemokine expressed in lymphoid tissues, selectively attracts B lymphocytes via BLR1\/CXCR5","volume":"187","author":"DF Legler","year":"1998","journal-title":"J Exp Med"},{"key":"ppat.1009831.ref053","doi-asserted-by":"crossref","first-page":"2702","DOI":"10.1073\/pnas.1520112113","article-title":"CXCL13 is a plasma biomarker of germinal center activity","author":"C Havenar-Daughton","year":"2016","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"ppat.1009831.ref054","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.it.2014.11.003","article-title":"Stromal infrastructure of the lymph node and coordination of immunity","volume":"36","author":"JE Chang","year":"2015","journal-title":"Trends Immunol"},{"key":"ppat.1009831.ref055","doi-asserted-by":"crossref","first-page":"6189","DOI":"10.4049\/jimmunol.181.9.6189","article-title":"Organizer-Like Reticular Stromal Cell Layer Common to Adult Secondary Lymphoid Organs","volume":"181","author":"T Katakai","year":"2008","journal-title":"The Journal of Immunology"},{"key":"ppat.1009831.ref056","doi-asserted-by":"crossref","first-page":"200","DOI":"10.3389\/fimmu.2012.00200","article-title":"Marginal reticular cells: a stromal subset directly descended from the lymphoid tissue organizer","volume":"3","author":"T. Katakai","year":"2012","journal-title":"Front Immunol"},{"key":"ppat.1009831.ref057","doi-asserted-by":"crossref","first-page":"2497","DOI":"10.1084\/jem.20111449","article-title":"Follicular dendritic cells help establish follicle identity and promote B cell retention in germinal centers","volume":"208","author":"X Wang","year":"2011","journal-title":"J Exp Med"},{"key":"ppat.1009831.ref058","doi-asserted-by":"crossref","first-page":"3734","DOI":"10.4049\/jimmunol.1103246","article-title":"Bcl6 and Maf cooperate to instruct human follicular helper CD4 T cell differentiation","volume":"188","author":"MA Kroenke","year":"2012","journal-title":"J Immunol"},{"key":"ppat.1009831.ref059","doi-asserted-by":"crossref","first-page":"1892","DOI":"10.1002\/eji.200636136","article-title":"Follicular B helper T cell activity is confined to CXCR5(hi)ICOS(hi) CD4 T cells and is independent of CD57 expression.","volume":"36","author":"A-U Rasheed","year":"2006","journal-title":"Eur J Immunol"},{"key":"ppat.1009831.ref060","first-page":"91","article-title":"CXCR5-Dependent Entry of CD8 T Cells into Rhesus Macaque B-Cell Follicles Achieved through T-Cell Engineering","author":"VI Ayala","year":"2017","journal-title":"J Virol"},{"key":"ppat.1009831.ref061","doi-asserted-by":"crossref","first-page":"492","DOI":"10.3389\/fimmu.2018.00492","article-title":"Simian Immunodeficiency Virus (SIV)-Specific Chimeric Antigen Receptor-T Cells Engineered to Target B Cell Follicles and Suppress SIV Replication.","volume":"9","author":"KP Haran","year":"2018","journal-title":"Front Immunol"},{"key":"ppat.1009831.ref062","doi-asserted-by":"crossref","first-page":"e27","DOI":"10.1002\/acg2.27","article-title":"Targeting reservoirs of HIV replication in lymphoid follicles with cellular therapies to cure HIV","volume":"2","author":"PJ Skinner","year":"2019","journal-title":"Advances in Cell and Gene Therapy"},{"key":"ppat.1009831.ref063","first-page":"00001","article-title":"Overcoming the immune privilege of B cell follicles to cure HIV-1 infection.","volume":"1","author":"PJ Skinner","year":"2014","journal-title":"J Hum Virol Retrovirol"},{"key":"ppat.1009831.ref064","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.jmoldx.2011.08.002","article-title":"RNAscope: a novel in situ RNA analysis platform for formalin-fixed, paraffin-embedded tissues","volume":"14","author":"F Wang","year":"2012","journal-title":"J Mol Diagn"},{"key":"ppat.1009831.ref065","doi-asserted-by":"crossref","first-page":"68","DOI":"10.20411\/pai.v1i1.100","article-title":"Defining HIV and SIV Reservoirs in Lymphoid Tissues.","volume":"1","author":"C Deleage","year":"2016","journal-title":"Pathogens & immunity"},{"key":"ppat.1009831.ref066","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1369\/0022155418756848","article-title":"Elucidating the burden of HIV in tissues using multiplexed immunofluorescence and in situ hybridization: Methods for the single-cell phenotypic characterization of cells harboring HIV in situ","volume":"66","author":"JJ Vasquez","year":"2018","journal-title":"J Histochem Cytochem"},{"key":"ppat.1009831.ref067","doi-asserted-by":"crossref","first-page":"9942","DOI":"10.1128\/JVI.01522-16","article-title":"Adoptive Transfer of Engineered Rhesus Simian Immunodeficiency Virus-Specific CD8 T Cells Reduces the Number of Transmitted\/Founder Viruses Established in Rhesus Macaques","author":"VI Ayala","year":"2016","journal-title":"Journal of Virology"},{"key":"ppat.1009831.ref068","doi-asserted-by":"crossref","first-page":"3","DOI":"10.4049\/jimmunol.1502372","article-title":"CCR7: Unifying Disparate Journeys to the Lymph Node","author":"GJ Randolph","year":"2016","journal-title":"Journal of immunology"},{"key":"ppat.1009831.ref069","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/S0092-8674(00)80059-8","article-title":"CCR7 coordinates the primary immune response by establishing functional microenvironments in secondary lymphoid organs","volume":"99","author":"R F\u00f6rster","year":"1999","journal-title":"Cell"},{"key":"ppat.1009831.ref070","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.omtm.2019.09.007","article-title":"Rapid Transduction and Expansion of Transduced T Cells with Maintenance of Central Memory Populations.","volume":"16","author":"MS Pampusch","year":"2020","journal-title":"Molecular Therapy\u2014Methods and Clinical Development"},{"key":"ppat.1009831.ref071","doi-asserted-by":"crossref","DOI":"10.1128\/JVI.76.2.875-884.2002","article-title":"Dominance of CD8 responses specific for epitopes bound by a single major histocompatibility complex class I molecule during the acute phase of viral infection","volume":"76","author":"BR Moth\u00e9","year":"2002","journal-title":"J Virol"},{"key":"ppat.1009831.ref072","first-page":"9","article-title":"The B-cell follicle in HIV infection: Barrier to a cure.","author":"MP Bronnimann","year":"2018","journal-title":"Front Immunol"},{"key":"ppat.1009831.ref073","first-page":"114","article-title":"Dynamics of SIV-specific CXCR5+ CD8 T cells during chronic SIV infection","author":"GH Mylvaganam","year":"2017","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ppat.1009831.ref074","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1038\/nature19317","article-title":"Follicular CXCR5-expressing CD8+ T cells curtail chronic viral infection","volume":"537","author":"R He","year":"2016","journal-title":"Nature"},{"key":"ppat.1009831.ref075","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1038\/mt.2015.19","article-title":"Lentivirus-mediated Gene Transfer in Hematopoietic Stem Cells Is Impaired in SHIV-infected, ART-treated Nonhuman Primates.","volume":"23","author":"PM Younan","year":"2015","journal-title":"Mol Ther"},{"key":"ppat.1009831.ref076","doi-asserted-by":"crossref","first-page":"194","DOI":"10.3389\/fimmu.2016.00194","article-title":"Microenvironmental control of high-speed interstitial T cell migration in the lymph node","volume":"7","author":"T Katakai","year":"2016","journal-title":"Front Immunol"},{"key":"ppat.1009831.ref077","first-page":"94","article-title":"HIV-1-Specific Chimeric Antigen Receptor T Cells Fail To Recognize and Eliminate the Follicular Dendritic Cell HIV Reservoir In Vitro","author":"MT Ollerton","year":"2020","journal-title":"J Virol"},{"key":"ppat.1009831.ref078","doi-asserted-by":"crossref","first-page":"4177","DOI":"10.1002\/(SICI)1521-4141(199812)28:12<4177::AID-IMMU4177>3.0.CO;2-J","article-title":"Characterization of T cell-expressed chimeric receptors with antibody-type specificity for the CD4 binding site of HIV-1 gp120","volume":"28","author":"N Bitton","year":"1998","journal-title":"Eur J Immunol"},{"key":"ppat.1009831.ref079","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1016\/0092-8674(91)90327-U","article-title":"Cellular immunity to HIV activated by CD4 fused to T cell or Fc receptor polypeptides","volume":"64","author":"C Romeo","year":"1991","journal-title":"Cell"},{"key":"ppat.1009831.ref080","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.virol.2013.08.002","article-title":"Anti-HIV designer T cells progressively eradicate a latently infected cell line by sequentially inducing HIV reactivation then killing the newly gp120-positive cells","volume":"446","author":"GK Sahu","year":"2013","journal-title":"Virology"},{"key":"ppat.1009831.ref081","doi-asserted-by":"crossref","first-page":"361","DOI":"10.3389\/fimmu.2020.00361","article-title":"Advances in Developing CAR T-Cell Therapy for HIV Cure.","volume":"11","author":"J Qi","year":"2020","journal-title":"Front Immunol"},{"key":"ppat.1009831.ref082","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1084\/jem.20040874","article-title":"CD4+ T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract","volume":"200","author":"JM Brenchley","year":"2004","journal-title":"J Exp Med"},{"key":"ppat.1009831.ref083","doi-asserted-by":"crossref","first-page":"95ra73","DOI":"10.1126\/scitranslmed.3002842","article-title":"T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia","volume":"3","author":"M Kalos","year":"2011","journal-title":"Sci Transl Med"},{"key":"ppat.1009831.ref084","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1186\/1479-5876-9-138","article-title":"Biomarkers in T cell therapy clinical trials","volume":"9","author":"M. Kalos","year":"2011","journal-title":"J Transl Med"},{"key":"ppat.1009831.ref085","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1056\/NEJMoa1103849","article-title":"Chimeric Antigen Receptor\u2013Modified T Cells in Chronic Lymphoid Leukemia","volume":"365","author":"DL Porter","year":"2011","journal-title":"N Engl J Med"},{"key":"ppat.1009831.ref086","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1158\/2159-8290.CD-17-1368","article-title":"Chimeric Antigen Receptor T Cell-Mediated Neurotoxicity in Nonhuman Primates.","volume":"8","author":"A Taraseviciute","year":"2018","journal-title":"Cancer Discov"},{"key":"ppat.1009831.ref087","doi-asserted-by":"crossref","first-page":"303","DOI":"10.4049\/jimmunol.0902413","article-title":"Trafficking, persistence, and activation state of adoptively transferred allogeneic and autologous Simian Immunodeficiency Virus-specific CD8(+) T cell clones during acute and chronic infection of rhesus macaques.","volume":"184","author":"DL Bolton","year":"2010","journal-title":"J Immunol"},{"key":"ppat.1009831.ref088","doi-asserted-by":"crossref","first-page":"315","DOI":"10.4049\/jimmunol.0902410","article-title":"Distribution, Persistence, and Efficacy of Adoptively Transferred Central and Effector Memory-Derived Autologous Simian Immunodeficiency Virus-Specific CD8+ T Cell Clones in Rhesus Macaques during Acute Infection","volume":"184","author":"JT Minang","year":"2010","journal-title":"The Journal of Immunology"},{"key":"ppat.1009831.ref089","first-page":"94","article-title":"Virologic and Immunologic Features of Simian Immunodeficiency Virus Control Post-ART Interruption in Rhesus Macaques","author":"Z Strongin","year":"2020","journal-title":"J Virol"},{"key":"ppat.1009831.ref090","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1038\/nature20583","article-title":"Ad26\/MVA therapeutic vaccination with TLR7 stimulation in SIV-infected rhesus monkeys","volume":"540","author":"EN Borducchi","year":"2016","journal-title":"Nature"},{"key":"ppat.1009831.ref091","article-title":"TLR7 agonists induce transient viremia and reduce the viral reservoir in SIV-infected rhesus macaques on antiretroviral therapy.","volume":"10","author":"S-Y Lim","year":"2018","journal-title":"Sci Transl Med"},{"key":"ppat.1009831.ref092","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1172\/JCI30973","article-title":"To ablate or not to ablate? HSCs in the T cell driver\u2019s seat","author":"C Anasetti","year":"2007","journal-title":"Journal of Clinical Investigation"},{"key":"ppat.1009831.ref093","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1172\/JCI32446","article-title":"Adoptive T cell therapy for cancer in the clinic","volume":"117","author":"CH June","year":"2007","journal-title":"J Clin Invest"},{"key":"ppat.1009831.ref094","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/S0065-2776(08)60778-6","article-title":"Adoptive T cell therapy of tumors: mechanisms operative in the recognition and elimination of tumor cells","volume":"49","author":"PD Greenberg","year":"1991","journal-title":"Adv Immunol"},{"key":"ppat.1009831.ref095","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1126\/science.1076514","article-title":"Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes","volume":"298","author":"ME Dudley","year":"2002","journal-title":"Science"},{"key":"ppat.1009831.ref096","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1182\/blood.2020006372","article-title":"Robust Expansion of HIV CAR T cells following antigen boosting in ART-suppressed nonhuman primates","volume":"136","author":"BJ Rust","year":"2020","journal-title":"Blood"},{"key":"ppat.1009831.ref097","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":"S Sengupta","year":"2018","journal-title":"Immunity"},{"key":"ppat.1009831.ref098","doi-asserted-by":"crossref","first-page":"410","DOI":"10.3389\/fcimb.2020.00410","article-title":"Engineering CAR T Cells to Target the HIV Reservoir.","volume":"10","author":"W Mu","year":"2020","journal-title":"Front Cell Infect Microbiol"},{"key":"ppat.1009831.ref099","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":"GM Webb","year":"2018","journal-title":"Blood Advances"},{"key":"ppat.1009831.ref100","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/srep31819","article-title":"The viral capping enzyme nsP1: a novel target for the inhibition of chikungunya virus infection.","volume":"6","author":"L Delang","year":"2016","journal-title":"Sci Rep"},{"key":"ppat.1009831.ref101","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1089\/hum.1996.7.8-913","article-title":"Comparison of efficiency of infection of human gene therapy target cells via four different retroviral receptors","volume":"7","author":"CD Porter","year":"1996","journal-title":"Hum Gene Ther"},{"key":"ppat.1009831.ref102","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1124\/jpet.107.123414","article-title":"Protection of mice from methotrexate toxicity by ex vivo transduction using lentivirus vectors expressing drug-resistant dihydrofolate reductase","volume":"322","author":"JL Gori","year":"2007","journal-title":"J Pharmacol Exp Ther"},{"key":"ppat.1009831.ref103","first-page":"1","article-title":"Transduction and expansion of primary T cells in nine days with maintenance of central memory phenotype.","volume":"2020","author":"MS Pampusch","year":"2020","journal-title":"J Vis Exp"},{"key":"ppat.1009831.ref104","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1111\/j.1600-0684.2005.00128.x","article-title":"Highly sensitive SIV plasma viral load assay: practical considerations, realistic performance expectations, and application to reverse engineering of vaccines for AIDS","volume":"34","author":"A Nichole Cline","year":"2005","journal-title":"J Med Primatol"},{"key":"ppat.1009831.ref105","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-019-10697-w","article-title":"Identification of HIV transmitting CD11c+ human epidermal dendritic cells.","volume":"10","author":"KM Bertram","year":"2019","journal-title":"Nat Commun"},{"key":"ppat.1009831.ref106","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s12575-014-0012-4","article-title":"Comparison of Vibratome and Compresstome sectioning of fresh primate lymphoid and genital tissues for in situ MHC-tetramer and immunofluorescence staining.","volume":"17","author":"HM Abdelaal","year":"2015","journal-title":"Biol Proced Online"},{"key":"ppat.1009831.ref107","doi-asserted-by":"crossref","first-page":"613","DOI":"10.4049\/jimmunol.165.2.613","article-title":"Cutting Edge: In Situ Tetramer Staining of Antigen-Specific T Cells in Tissues","volume":"165","author":"PJ Skinner","year":"2000","journal-title":"The Journal of Immunology"},{"key":"ppat.1009831.ref108","first-page":"1","article-title":"In Situ MHC-tetramer Staining and Quantitative Analysis to Determine the Location, Abundance, and Phenotype of Antigen-specific CD8 T Cells in Tissues Video Link.","author":"S Li","year":"2017","journal-title":"J Vis Exp"},{"key":"ppat.1009831.ref109","doi-asserted-by":"crossref","DOI":"10.3390\/ijms20205165","article-title":"Detection of Antigen-Specific T Cells Using In Situ MHC Tetramer Staining.","volume":"20","author":"HM Abdelaal","year":"2019","journal-title":"Int J Mol Sci"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1009831","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,2,17]],"date-time":"2022-02-17T00:00:00Z","timestamp":1645056000000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1009831","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,26]],"date-time":"2023-01-26T00:54:24Z","timestamp":1674694464000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1009831"}},"subtitle":[],"editor":[{"given":"Daniel C.","family":"Douek","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,2,7]]},"references-count":109,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,2,7]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1009831","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.07.26.453803","asserted-by":"object"}]},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,7]]}}}