{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T17:58:18Z","timestamp":1791655098616,"version":"4.3.4"},"update-to":[{"DOI":"10.1371\/journal.ppat.1012717","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T00:00:00Z","timestamp":1753660800000}}],"reference-count":40,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T00:00:00Z","timestamp":1752796800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82341071 and 81871239"],"award-info":[{"award-number":["82341071 and 81871239"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82272331"],"award-info":[{"award-number":["82272331"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015401","name":"Key Research and Development Projects of Shaanxi Province","doi-asserted-by":"publisher","award":["2023-JC-ZD-49"],"award-info":[{"award-number":["2023-JC-ZD-49"]}],"id":[{"id":"10.13039\/501100015401","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015401","name":"Key Research and Development Projects of Shaanxi Province","doi-asserted-by":"publisher","award":["2022JZ-45"],"award-info":[{"award-number":["2022JZ-45"]}],"id":[{"id":"10.13039\/501100015401","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015401","name":"Key Research and Development Projects of Shaanxi Province","doi-asserted-by":"publisher","award":["2023IC-YB-640"],"award-info":[{"award-number":["2023IC-YB-640"]}],"id":[{"id":"10.13039\/501100015401","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015401","name":"Key Research and Development Projects of Shaanxi Province","doi-asserted-by":"publisher","award":["2024SF-YBXM-286"],"award-info":[{"award-number":["2024SF-YBXM-286"]}],"id":[{"id":"10.13039\/501100015401","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    NK cells could participate in the pathogenesis process of virus infectious diseases through the inhibitory receptor CD94\/NKG2A interacting with HLA-E\/virus-derived peptide complex. However, the effects and mechanisms of NKG2A-HLA-E axis-mediated NK cell responses in hemorrhagic fever with renal syndrome (HFRS) caused by Hantaan virus (HTNV) infection remain unclear. Single-cell RNA sequencing and flow cytometry were employed to analyze the phenotype and function of different NK cell subsets in HFRS patients. The K562\/HLA-E cells binding assay was used for peptide affinity detection. The binding capacity of HLA-E\/peptide-CD94\/NKG2A was detected using ligand-receptor binding assay and tetramer staining. The cytotoxicity assay of NK cells against peptide-pulsed K562\/HLA-E cells was conducted for functional evaluation. In this study, CD56\n                    <jats:sup>dim<\/jats:sup>\n                    CD16\n                    <jats:sup>+<\/jats:sup>\n                    NKG2A\n                    <jats:sup>+<\/jats:sup>\n                    NK cells were the main subset in HFRS patients, showing activation and proliferation phenotypes with NKG2C\n                    <jats:sup>-<\/jats:sup>\n                    CD57\n                    <jats:sup>-<\/jats:sup>\n                    and the ability to secrete tumor necrosis factor-\u03b1 (TNF-\u03b1), interferon-\u03b3 (IFN-\u03b3) and cytotoxic mediators. Notably, none of the four identified HTNV epitopes presented by HLA-E could be recognized by CD94\/NKG2A on CD56\n                    <jats:sup>dim<\/jats:sup>\n                    NKG2A\n                    <jats:sup>+<\/jats:sup>\n                    NK cells. Furthermore, the subset of CD56\n                    <jats:sup>dim<\/jats:sup>\n                    NKG2A\n                    <jats:sup>+<\/jats:sup>\n                    NK cells showed the enhanced cytolytic capacity against HTNV peptide pulsed K562\/HLA-E cells\n                    <jats:italic>ex vivo<\/jats:italic>\n                    . Taken together, the findings demonstrate that HTNV-derived peptides presented by HLA-E could \u201cabrogate\u201d the inhibition of CD56\n                    <jats:sup>dim<\/jats:sup>\n                    NKG2A\n                    <jats:sup>+<\/jats:sup>\n                    NK cells, contributing to the antiviral immune response in HFRS patients.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1012717","type":"journal-article","created":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T17:50:14Z","timestamp":1752861014000},"page":"e1012717","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Hantaan virus-derived peptides that stabilize HLA-E could abrogate inhibition of CD56dimNKG2A+ NK cells"],"prefix":"10.1371","volume":"21","author":[{"given":"Manling","family":"Xue","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyue","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunmei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajia","family":"Zuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fenglan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiyue","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuyang","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Zhuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boquan","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1936-3982","authenticated-orcid":true,"given":"Ying","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,7,18]]},"reference":[{"issue":"9","key":"ppat.1012717.ref001","article-title":"Hantavirus 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