{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:53:44Z","timestamp":1790834024527,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,8,20]],"date-time":"2017-08-20T00:00:00Z","timestamp":1503187200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009139","name":"Deutsches Zentrum f\u00fcr Infektionsforschung","doi-asserted-by":"publisher","award":["DZIF TTU\u201005\u2010702"],"award-info":[{"award-number":["DZIF TTU\u201005\u2010702"]}],"id":[{"id":"10.13039\/100009139","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["DFG SU 888\/1\u20101"],"award-info":[{"award-number":["DFG SU 888\/1\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>\n                      Hepatitis E virus (\n                      <jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content>\n                      ) is a major cause of acute viral hepatitis with &gt;3 million symptomatic cases per year accounting for 70\u00a0000\n                      <jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content>\n                      \u2010related deaths.\n                      <jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content>\n                      \u2010specific T\u2010cell responses have been investigated against structural proteins expressed by open reading frames (\n                      <jats:styled-content style=\"fixed-case\">ORF<\/jats:styled-content>\n                      ) 2 and 3. T\u2010cell responses against non\u2010structural\n                      <jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content>\n                      proteins encoded by\n                      <jats:styled-content style=\"fixed-case\">ORF<\/jats:styled-content>\n                      1 are hardly studied. The aim of this study was to determine\n                      <jats:styled-content style=\"fixed-case\">HEV ORF<\/jats:styled-content>\n                      1\u2010specific T\u2010cell responses in comparison to\n                      <jats:styled-content style=\"fixed-case\">ORF<\/jats:styled-content>\n                      2\/3 in patients exposed to\n                      <jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      <jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content>\n                      \u2010specific\n                      <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>\n                      4\n                      <jats:sup>+<\/jats:sup>\n                      and\n                      <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>\n                      8\n                      <jats:sup>+<\/jats:sup>\n                      T\u2010cell responses against\n                      <jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content>\n                      genotype 3 were investigated in patients with acute and chronic hepatitis E as well as in\n                      <jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content>\n                      seropositive and seronegative individuals.\n                      <jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content>\n                      \u2010specific T\u2010cell responses were determined by proliferation and intracellular cytokine assay upon stimulation of\n                      <jats:styled-content style=\"fixed-case\">PBMC<\/jats:styled-content>\n                      s with\n                      <jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content>\n                      \u2010specific overlapping peptide pools spanning the entire\n                      <jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content>\n                      genome.\n                      <jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content>\n                      \u2010antigen was measured using an anti\u2010\n                      <jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content>\n                      antigen\u2010specific\n                      <jats:styled-content style=\"fixed-case\">ELISA<\/jats:styled-content>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Broad\n                      <jats:styled-content style=\"fixed-case\">HEV ORF<\/jats:styled-content>\n                      1\u2010specific T\u2010cell responses were detected in patients with acute, resolved and chronic hepatitis E without distinct dominant regions. The magnitude and frequency in recognition of\n                      <jats:styled-content style=\"fixed-case\">ORF<\/jats:styled-content>\n                      1\u2010specific T\u2010cell responses were similar compared to responses against\n                      <jats:styled-content style=\"fixed-case\">HEV ORF<\/jats:styled-content>\n                      2\/3. Longitudinal studies of\n                      <jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content>\n                      \u2010specific T\u2010cell responses displayed similar behaviour against structural and non\u2010structural proteins.\n                      <jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content>\n                      \u2010antigen levels were inversely correlated with\n                      <jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content>\n                      \u2010specific T\u2010cell responses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      <jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content>\n                      \u2010specific T\u2010cell responses are detectable against the entire\n                      <jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content>\n                      genome including the non\u2010structural proteins.\n                      <jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content>\n                      \u2010specific T\u2010cell responses are associated with control of\n                      <jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content>\n                      infection. These findings have implications for the design of\n                      <jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content>\n                      vaccines.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.13521","type":"journal-article","created":{"date-parts":[[2017,7,18]],"date-time":"2017-07-18T11:32:39Z","timestamp":1500377559000},"page":"266-277","source":"Crossref","is-referenced-by-count":24,"title":["Hepatitis E virus\n                    <scp>ORF<\/scp>\n                    1 induces proliferative and functional T\u2010cell responses in patients with ongoing and resolved hepatitis E"],"prefix":"10.1111","volume":"38","author":[{"given":"Jana","family":"Al\u2010Ayoubi","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Endocrinology Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Behrendt","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Endocrinology Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgit","family":"Bremer","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Endocrinology Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pothakamuri Venkata","family":"Suneetha","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Endocrinology Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anett","family":"Gisa","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Endocrinology Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska","family":"Rinker","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Endocrinology Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"Manns","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Endocrinology Hannover Medical School  Hannover Germany"},{"name":"German Center for Infection Research (DZIF)  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Cornberg","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Endocrinology Hannover Medical School  Hannover Germany"},{"name":"German Center for Infection Research (DZIF)  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2906-0480","authenticated-orcid":false,"given":"Heiner","family":"Wedemeyer","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Endocrinology Hannover Medical School  Hannover Germany"},{"name":"German Center for Infection Research (DZIF)  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9666-0753","authenticated-orcid":false,"given":"Anke R. 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