{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T20:55:42Z","timestamp":1780606542190,"version":"3.54.1"},"reference-count":154,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,8,6]],"date-time":"2023-08-06T00:00:00Z","timestamp":1691280000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Chronic hepatitis C virus (HCV) infections compromise natural killer (NK)\u2010cell immunity. Direct\u2010acting antivirals (DAA) effectively eliminate HCV, but the long\u2010term effects on NK cells in cured patients are debated. We conducted a proteomic study on CD56\n                    <jats:sup>+<\/jats:sup>\n                    NK cells of chronic HCV\u2010infected patients before and 1 year after DAA therapy. Donor\u2010variation was observed in NK\u2010cell proteomes of HCV\u2010infected patients, with 46 dysregulated proteins restored after DAA therapy. However, 30% of the CD56\n                    <jats:sup>+<\/jats:sup>\n                    NK\u2010cell proteome remained altered 1 year post\u2010therapy, indicating a phenotypic shift with low donor\u2010variation. NK cells from virus\u2010negative cured patients exhibited global regulation of RNA\u2010processing and pathways related to \u201cstimuli response\u201d, \u201cchemokine signaling\u201d, and \u201ccytotoxicity regulation\u201d. Proteomics identified downregulation of vesicle transport components (CD107a, COPI\/II complexes) and altered receptor expression profiles, indicating an inhibited NK\u2010cell phenotype. Yet, activated NK cells from HCV patients before and after therapy effectively upregulated IFN\u2010\u03b3 and recruited CD107a. Conversely, reduced surface expression levels of Tim\u20103 and 2B4 were observed before and after therapy. In conclusion, this study reveals long\u2010term effects on the CD56\n                    <jats:sup>+<\/jats:sup>\n                    NK\u2010cell compartment in convalescent HCV patients 1 year after therapy, with limited abundance of vesicle transport complexes and surface receptors, associated with a responsive NK\u2010cell phenotype.\n                  <\/jats:p>","DOI":"10.1002\/eji.202250291","type":"journal-article","created":{"date-parts":[[2023,7,29]],"date-time":"2023-07-29T07:04:56Z","timestamp":1690614296000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Proteomics reveals a global phenotypic shift of NK cells in HCV patients treated with direct\u2010acting antivirals"],"prefix":"10.1002","volume":"53","author":[{"given":"Wenjie","family":"Bi","sequence":"first","affiliation":[{"name":"Key Laboratory of Infection and Immunity of Shandong Province &amp; Department of Immunology School of Basic Medical Sciences Shandong University Jinan Shandong P. 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