{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T21:22:49Z","timestamp":1772227369095,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.ppat.1011107","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T00:00:00Z","timestamp":1675209600000}}],"reference-count":55,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T00:00:00Z","timestamp":1674172800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["F30-HD100170-01A1"],"award-info":[{"award-number":["F30-HD100170-01A1"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014264","name":"Triangle Center for Evolutionary Medicine","doi-asserted-by":"crossref","award":["Graduate Student Award"],"award-info":[{"award-number":["Graduate Student Award"]}],"id":[{"id":"10.13039\/100014264","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100015487","name":"National CMV Foundation","doi-asserted-by":"publisher","award":["Early Career Award"],"award-info":[{"award-number":["Early Career Award"]}],"id":[{"id":"10.13039\/100015487","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000928","name":"Welch Foundation","doi-asserted-by":"publisher","award":["F-0003-19620604"],"award-info":[{"award-number":["F-0003-19620604"]}],"id":[{"id":"10.13039\/100000928","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","award":["R21-AI147992-01"],"award-info":[{"award-number":["R21-AI147992-01"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Medearis CMV Scholars Program"}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Cytomegalovirus (CMV) is a leading cause of infant hearing loss and neurodevelopmental delay, but there are no clinically licensed vaccines to prevent infection, in part due to challenges eliciting neutralizing antibodies. One of the most well-studied targets for CMV vaccines is the viral fusogen glycoprotein B (gB), which is required for viral entry into host cells. Within gB, antigenic domain 2 site 1 (AD-2S1) is a target of potently neutralizing antibodies, but gB-based candidate vaccines have yet to elicit robust responses against this region. We mapped the genealogy of B cells encoding potently neutralizing anti-gB AD-2S1 antibodies from their inferred unmutated common ancestor (UCA) and characterized the binding and function of early lineage ancestors. Surprisingly, we found that a single amino acid heavy chain mutation A33N, which was an improbable mutation rarely generated by somatic hypermutation machinery, conferred broad CMV neutralization to the non-neutralizing UCA antibody. Structural studies revealed that this mutation mediated key contacts with the gB AD-2S1 epitope. Collectively, these results provide insight into potently neutralizing gB-directed antibody evolution in a single donor and lay a foundation for using this B cell-lineage directed approach for the design of next-generation CMV vaccines.<\/jats:p>","DOI":"10.1371\/journal.ppat.1011107","type":"journal-article","created":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T14:04:20Z","timestamp":1674223460000},"page":"e1011107","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["A single, improbable B cell receptor mutation confers potent neutralization against cytomegalovirus"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6865-5615","authenticated-orcid":true,"given":"Jennifer A.","family":"Jenks","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharmi","family":"Amin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madeline R.","family":"Sponholtz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amit","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Wrapp","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sravani","family":"Venkatayogi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joshua J.","family":"Tu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krithika","family":"Karthigeyan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah M.","family":"Valencia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Megan","family":"Connors","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa J.","family":"Harnois","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bhavna","family":"Hora","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Rochat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason S.","family":"McLellan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin","family":"Wiehe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1438-4554","authenticated-orcid":true,"given":"Sallie R.","family":"Permar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,1,20]]},"reference":[{"issue":"6","key":"ppat.1011107.ref001","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1097\/TP.0000000000002191","article-title":"The Third International Consensus Guidelines on the Management of Cytomegalovirus in Solid-organ Transplantation","volume":"102","author":"CN Kotton","year":"2018","journal-title":"Transplantation"},{"issue":"6","key":"ppat.1011107.ref002","doi-asserted-by":"crossref","first-page":"e177","DOI":"10.1016\/S1473-3099(17)30143-3","article-title":"Congenital cytomegalovirus infection in pregnancy and the neonate: consensus recommendations for prevention, diagnosis, and therapy","volume":"17","author":"WD Rawlinson","year":"2017","journal-title":"Lancet Infect Dis"},{"issue":"10","key":"ppat.1011107.ref003","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1056\/NEJM199203053261003","article-title":"The outcome of congenital cytomegalovirus infection in relation to maternal antibody status","volume":"326","author":"KB Fowler","year":"1992","journal-title":"N Engl J Med"},{"issue":"20","key":"ppat.1011107.ref004","doi-asserted-by":"crossref","first-page":"2151","DOI":"10.1056\/NEJMra050700","article-title":"Newborn hearing screening\u2014a silent revolution","volume":"354","author":"CC Morton","year":"2006","journal-title":"N Engl J Med"},{"key":"ppat.1011107.ref005","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.mad.2015.09.003","article-title":"The silent war of CMV in aging and HIV infection","volume":"158","author":"RB Effros","year":"2016","journal-title":"Mech Ageing Dev"},{"key":"ppat.1011107.ref006","unstructured":"In: Stratton KR, Durch JS, Lawrence RS, editors. 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