{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T01:51:39Z","timestamp":1776995499464,"version":"3.51.4"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,1,25]],"date-time":"2018-01-25T00:00:00Z","timestamp":1516838400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000085","name":"Ontario HIV Treatment Network","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000085","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008220","name":"Canadian Foundation for AIDS Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008220","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Clearance of hepatitis C virus (<jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>) is dependent on an effective virus\u2010specific <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>8<jats:sup>+<\/jats:sup> T\u2010cell response, which is dysfunctional in chronic <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> infection. Dysfunction in bulk or non\u2010<jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>\u2010specific <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>8<jats:sup>+<\/jats:sup> T\u2010cells in <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> infection has also been observed. This may contribute to observed reductions in immunity to other diseases (e.g. cancer, viral co\u2010infections) in <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>\u2010infected individuals. Evidence suggests that the <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> core protein (found in blood as free protein) may contribute to this impairment. To determine if <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> core contributes to the impairment of effector functions and survival potential of <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>8<jats:sup>+<\/jats:sup> T\u2010cells, isolated human <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>8<jats:sup>+<\/jats:sup> T\u2010cells from healthy donors were pre\u2010incubated with recombinant <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> core protein for 72 hr and then stimulated <jats:italic>in vitro<\/jats:italic> to evaluate proliferation, survival potential and effector functions. Pre\u2010incubation of stimulated <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>8<jats:sup>+<\/jats:sup> T\u2010cells with <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> core significantly reduced their proliferation. Perforin production and degranulation were also decreased, but interferon\u2010<jats:italic>\u03b3<\/jats:italic> production was unchanged. Additionally, when <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>8<jats:sup>+<\/jats:sup> T\u2010cells were treated with serum from <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content><jats:sup>+<\/jats:sup> individuals, they produced less perforin than cells treated with healthy serum. Up\u2010regulation of anti\u2010apoptotic Bcl\u20102 was slightly lower in cells treated with <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> core, but signal transducer and activator of transcription 5 (<jats:styled-content style=\"fixed-case\">STAT<\/jats:styled-content>5) activation was increased, suggesting dysregulation downstream of <jats:styled-content style=\"fixed-case\">STAT<\/jats:styled-content> activation. Our study reveals that <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> core reduces the activity and target lysis\u2010associated functions of <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>8<jats:sup>+<\/jats:sup> T\u2010cells. This may contribute to the generalized impairment of <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>8<jats:sup>+<\/jats:sup> T\u2010cells observed in <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> infection. These findings provide insight for the design of novel counteractive immune\u2010mediated strategies including the design of effective therapeutic vaccines for use in <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content><jats:sup>+<\/jats:sup> individuals.<\/jats:p>","DOI":"10.1111\/imm.12882","type":"journal-article","created":{"date-parts":[[2017,12,20]],"date-time":"2017-12-20T09:03:05Z","timestamp":1513760585000},"page":"156-165","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Hepatitis C virus core protein reduces <scp>CD<\/scp>8<sup>+<\/sup> T\u2010cell proliferation, perforin production and degranulation but increases <scp>STAT<\/scp>5 activation"],"prefix":"10.1111","volume":"154","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6578-8471","authenticated-orcid":false,"given":"Sarwat Tahsin","family":"Khan","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Microbiology and Immunology University of Ottawa Ottawa ON Canada"},{"name":"Chronic Diseases Programme Ottawa Hospital Research Institute Ottawa ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Winston","family":"Karges","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Microbiology and Immunology University of Ottawa Ottawa ON Canada"},{"name":"Chronic Diseases Programme Ottawa Hospital Research Institute Ottawa ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Curtis L.","family":"Cooper","sequence":"additional","affiliation":[{"name":"School of Epidemiology Public Health and Preventative Medicine University of Ottawa Ottawa ON Canada"},{"name":"Division of Infectious Diseases The Ottawa Hospital Ottawa ON Canada"},{"name":"Clinical Epidemiology Programme Ottawa Hospital Research Institute Ottawa ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela M.","family":"Crawley","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Microbiology and Immunology University of Ottawa Ottawa ON Canada"},{"name":"Chronic Diseases Programme Ottawa Hospital Research Institute Ottawa ON Canada"},{"name":"Department of Biology Carleton University Ottawa ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,1,25]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1711.2001.01036.x"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/692408"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.12.6409-6419.2004"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510260703"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-979468"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.6.3447"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1089\/vim.2006.0096"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0077008"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.3.1744"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0157055"},{"key":"e_1_2_9_12_1","doi-asserted-by":"crossref","first-page":"931","DOI":"10.4049\/jimmunol.162.2.931","article-title":"Suppression of host immune response by the core protein of hepatitis C virus: possible implications for hepatitis C virus persistence","volume":"162","author":"Large MK","year":"1999","journal-title":"J Immunol"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.4.2230-2239.2005"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1645"},{"key":"e_1_2_9_15_1","volume-title":"Hepatitis C Viruses: Genomes and Molecular Biology","author":"Polyak SJ","year":"2006"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840190206"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-010-0351-5"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.17.8240-8250.2001"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI10323"},{"key":"e_1_2_9_20_1","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.4049\/jimmunol.153.4.1430","article-title":"Human T\u2010cells express specific binding sites for C1q. Role in T cell activation and proliferation","volume":"153","author":"Chen A","year":"1994","journal-title":"J Immunol"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2008.02829.x"},{"key":"e_1_2_9_22_1","article-title":"Hepatitis C virus core protein inhibits human T lymphocyte responses by a complement\u2010dependent regulatory pathway","volume":"167","author":"Yao ZQ","year":"2001","journal-title":"J Immunol"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxn120"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2010.00911.x"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1615\/CritRevImmunol.v28.i4.40"},{"key":"e_1_2_9_26_1","volume-title":"Janeway's Immunobiology","author":"Murphy K","year":"2012"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0313122"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20040789"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2008.00745.x"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0602565103"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0103219"}],"container-title":["Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fimm.12882","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/imm.12882","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T09:53:42Z","timestamp":1695549222000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/imm.12882"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,1,25]]},"references-count":30,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018,5]]}},"alternative-id":["10.1111\/imm.12882"],"URL":"https:\/\/doi.org\/10.1111\/imm.12882","archive":["Portico"],"relation":{},"ISSN":["0019-2805","1365-2567"],"issn-type":[{"value":"0019-2805","type":"print"},{"value":"1365-2567","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,1,25]]},"assertion":[{"value":"2017-05-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-12-12","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-01-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}