{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T07:59:54Z","timestamp":1722931194330},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2016,2,1]],"date-time":"2016-02-01T00:00:00Z","timestamp":1454284800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["510448","1016351","1043067"],"award-info":[{"award-number":["510448","1016351","1043067"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Viral Hepatitis"],"published-print":{"date-parts":[[2016,6]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Injecting drug use remains the major risk factor for hepatitis C (<jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>) transmission. A minority of long\u2010term injecting drug users remain seronegative and aviraemic, despite prolonged exposure to <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> \u2013 termed highly exposed seronegative subjects. Natural killer (NK) cells have been implicated in this apparent protection. A longitudinal nested, three group case\u2013control series of subjects was selected from a prospective cohort of seronegative injecting drug users who became incident cases (<jats:italic>n<\/jats:italic> = 11), remained seronegative (<jats:italic>n<\/jats:italic> = 11) or reported transient high\u2010risk behaviour and remained uninfected (<jats:italic>n<\/jats:italic> = 11). The groups were matched by age, sex and initial risk behaviour characteristics. Stored peripheral blood mononuclear cells were assayed in multicolour flow cytometry to enumerate natural killer cell subpopulations and to assess functional activity using Toll\u2010like receptor ligands before measurement of activation, cytokine production and natural cytotoxicity receptor expression. Principal components were derived to describe the detailed phenotypic characteristics of the major <jats:styled-content style=\"fixed-case\">NK<\/jats:styled-content> subpopulations (based on <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>56 and <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>16 co\u2010expression), before logistic regression analysis to identify associations with exposed, seronegative individuals. The <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>56<jats:sup>dim<\/jats:sup><jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>16<jats:sup>+<\/jats:sup> (<jats:italic>P<\/jats:italic> = 0.05, <jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content> 6.92) and <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>56<jats:sup>dim<\/jats:sup><jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>16<jats:sup>\u2212<\/jats:sup> (<jats:italic>P<\/jats:italic> = 0.05, <jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content> 6.07) principal components differed between exposed, seronegative individuals and pre\u2010infection samples of the other two groups. These included <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>56<jats:sup>dim<\/jats:sup><jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>16<jats:sup>+<\/jats:sup> and <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>56<jats:sup>dim<\/jats:sup><jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>16<jats:sup>\u2212<\/jats:sup> subsets with <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>56<jats:sup>dim<\/jats:sup><jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>16<jats:sup>+<\/jats:sup> <jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>\u2010<jats:italic>\u03b3<\/jats:italic> and <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u2010<jats:italic>\u03b1<\/jats:italic> on unstimulated cells, and <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>56<jats:sup>dim<\/jats:sup><jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>16<jats:sup>\u2212<\/jats:sup> <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>69<jats:sup>+<\/jats:sup>, <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>107a<jats:sup>+<\/jats:sup>, <jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>\u2010<jats:italic>\u03b3<\/jats:italic> and <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u2010<jats:italic>\u03b1<\/jats:italic> following <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content> stimulation. The cytotoxic <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>56<jats:sup>dim<\/jats:sup> <jats:styled-content style=\"fixed-case\">NK<\/jats:styled-content> subset thus distinguished highly exposed, seronegative subjects, suggesting <jats:styled-content style=\"fixed-case\">NK<\/jats:styled-content> cytotoxicity may contribute to protection from <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> acquisition. Further investigation of the determinants of this association and prospective assessment of protection against <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> infection are warranted.<\/jats:p>","DOI":"10.1111\/jvh.12511","type":"journal-article","created":{"date-parts":[[2016,2,1]],"date-time":"2016-02-01T12:07:41Z","timestamp":1454328461000},"page":"464-472","source":"Crossref","is-referenced-by-count":3,"title":["Natural killer cells in highly exposed hepatitis C\u2010seronegative injecting drug users"],"prefix":"10.1111","volume":"23","author":[{"given":"M. M.","family":"Mina","sequence":"first","affiliation":[{"name":"Inflammation and Infection Research Centre School of Medical Sciences University of New South Wales Sydney Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B.","family":"Cameron","sequence":"additional","affiliation":[{"name":"Inflammation and Infection Research Centre School of Medical Sciences University of New South Wales Sydney Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.","family":"Luciani","sequence":"additional","affiliation":[{"name":"Inflammation and Infection Research Centre School of Medical Sciences University of New South Wales Sydney Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"U.","family":"Vollmer\u2010Conna","sequence":"additional","affiliation":[{"name":"School of Psychiatry University of New South Wales Sydney Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. 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