{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T18:14:19Z","timestamp":1790705659210,"version":"4.1.0"},"reference-count":63,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2016,10,28]],"date-time":"2016-10-28T00:00:00Z","timestamp":1477612800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2016,12]]},"abstract":"<jats:p>\n                    The interplay between host antiviral immunity and immunopathology during hepatitis E virus (HEV) infection determines important clinical outcomes. We characterized the specificity, functionality, and durability of host T\u2010cell responses against the full\u2010length HEV virus and assessed a novel \u201cQuantiferon\u201d assay for the rapid diagnosis of HEV infection. Eighty\u2010nine volunteers were recruited from Oxford, Truro (UK), and Toulouse (France), including 44 immune\u2010competent patients with acute HEV infection, 18 HEV\u2010exposed immunosuppressed organ\u2010transplant recipients (8 with chronic HEV), and 27 healthy volunteers. A genotype 3a peptide library (616 overlapping peptides spanning open reading frames [ORFs] 1\u20103) was used in interferon\u2010gamma (IFN\u2010\u03b3) T\u2010cell ELISpot assays. CD4\n                    <jats:sup>+<\/jats:sup>\n                    \/CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell subsets and polyfunctionality were defined using ICCS and SPICE analysis. Quantification of IFN\u2010\u03b3 used whole\u2010blood stimulation with recombinant HEV\u2010capsid protein in the QuantiFERON kit. HEV\u2010specific T\u2010cell responses were detected in 41\/44 immune\u2010competent HEV exposed volunteers (median magnitude: 397 spot\u2010forming units\/10\n                    <jats:sup>6<\/jats:sup>\n                    peripheral blood mononuclear cells), most frequently targeting ORF2. High\u2010magnitude, polyfunctional CD4 and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells were detected during acute disease and maintained to 12 years, but these declined over time, with CD8\n                    <jats:sup>+<\/jats:sup>\n                    responses becoming more monofunctional. Low\u2010level responses were detectable in immunosuppressed patients. Twenty\u2010three novel HEV CD4\n                    <jats:sup>+<\/jats:sup>\n                    and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell targets were mapped predominantly to conserved genomic regions. QuantiFERON testing demonstrated an inverse correlation between IFN\u2010\u03b3 production and the time from clinical presentation, providing 100% specificity, and 71% sensitivity (area under the receiver operator characteristic curve of 0.86) for HEV exposure at 0.3 IU\/mL.\n                    <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic>\n                    Robust HEV\u2010specific T\u2010cell responses generated during acute disease predominantly target ORF2, but decline in magnitude and polyfunctionality over time. Defining HEV T\u2010cell targets will be important for the investigation of HEV\u2010associated autoimmune disease. (H\n                    <jats:sc>epatology<\/jats:sc>\n                    2016;64:1934\u20101950).\n                  <\/jats:p>","DOI":"10.1002\/hep.28819","type":"journal-article","created":{"date-parts":[[2016,9,15]],"date-time":"2016-09-15T18:57:05Z","timestamp":1473965825000},"page":"1934-1950","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":59,"title":["Characterization of the Specificity, Functionality, and Durability of Host T\u2010Cell Responses Against the Full\u2010Length Hepatitis E Virus"],"prefix":"10.1097","volume":"64","author":[{"given":"Anthony","family":"Brown","sequence":"first","affiliation":[{"name":"Peter Medawar Building for Pathogen Research,University of Oxford,Oxford,United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John S.","family":"Halliday","sequence":"additional","affiliation":[{"name":"Peter Medawar Building for Pathogen Research,University of Oxford,Oxford,United Kingdom"},{"name":"The Royal Melbourne Hospital,Melbourne,Victoria,Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo","family":"Swadling","sequence":"additional","affiliation":[{"name":"Peter Medawar Building for Pathogen Research,University of Oxford,Oxford,United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richie G.","family":"Madden","sequence":"additional","affiliation":[{"name":"The Royal Cornwall Hospital,Truro,United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Bendall","sequence":"additional","affiliation":[{"name":"The Royal Cornwall Hospital,Truro,United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy G.","family":"Hunter","sequence":"additional","affiliation":[{"name":"The Royal Cornwall Hospital,Truro,United 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Building for Pathogen Research,University of Oxford,Oxford,United Kingdom"},{"name":"Centre for Tropical Medicine & Global Health,University of Oxford,Oxford,United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Klenerman","sequence":"additional","affiliation":[{"name":"Peter Medawar Building for Pathogen Research,University of Oxford,Oxford,United Kingdom"},{"name":"Oxford University Hospitals NHS Foundation Trust,Oxford,United Kingdom"},{"name":"National Institute for Health Research (NIHR),Oxford Biomedical Research Centre,Oxford,United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques","family":"Izopet","sequence":"additional","affiliation":[{"name":"The Rangueil Hospital,Toulouse,France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nassim","family":"Kamar","sequence":"additional","affiliation":[{"name":"The Rangueil 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