{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T06:16:45Z","timestamp":1773296205457,"version":"3.50.1"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":200,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000272","name":"NIHR","doi-asserted-by":"crossref","award":["DRF-2010-03-29"],"award-info":[{"award-number":["DRF-2010-03-29"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2015,4]]},"abstract":"<jats:p>Emerging therapies for chronic hepatitis C viral (HCV) infection involve inhibition of viral enzymes with drug combinations. Natural, or treatment\u2010induced, enzyme polymorphisms reduce efficacy. We developed a phenotyping assay to aid drug selection based on viral transfer from monocytes to hepatocytes. We studied HCV in monocytes from infected patients and developed a model in which patient\u2010derived HCV is \u201ccaptured\u201d by the cell line THP\u20101 and replication assessed after fusion to hepatoma cells. We found that monocytes from HCV\u2010infected patients harbor virus that replicates when cells are fused to hepatocytes. THP\u20101 cells incubated with infected sera capture HCV, which replicates when fused to hepatocytes. Inhibitable replication of all HCV genotypes was achieved (42 of 52 isolates). We measured sensitivity of telaprevir (TVR) and alisporivir (AVR) in different genotypes, and showed differences in 50% inhibitory concentration (IC<jats:sub>50<\/jats:sub>) correlating with clinical response (TVR IC<jats:sub>50<\/jats:sub> for genotype (G)1 was 0.042 \u00b1 0.003 vs. 0.117 \u00b1 0.015 \u03bcM for G3, whereas AVR IC<jats:sub>50<\/jats:sub> for G1 was 0.139 \u00b1 0.013 vs. 0.044 \u00b1 0.007 \u03bcM for G3). We tested TVR\u2010resistant viral isolates and identified changes in IC<jats:sub>50<\/jats:sub>. One patient with a poor clinical response to TVR and wild\u2010type viral sequence showed reduced TVR sensitivity in our assay. We studied samples from a 2\u2010week TVR monotherapy study in which 5 of 8 patients with G3 HCV did not respond whereas 3 of 8 patients did. The \u201ccapture\u2010fusion\u201d assay correctly identified responders. <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>: The capture\u2010fusion model represents a promising new technique that may help identify appropriate treatment strategies for patients with chronic HCV infection. (H<jats:sc>epatology<\/jats:sc> 2015;61:1192\u20131204)<\/jats:p>","DOI":"10.1002\/hep.27570","type":"journal-article","created":{"date-parts":[[2014,10,20]],"date-time":"2014-10-20T09:29:26Z","timestamp":1413797366000},"page":"1192-1204","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":4,"title":["Development and validation of a \u201ccapture\u2010fusion\u201d model to study drug sensitivity of patient\u2010derived hepatitis C"],"prefix":"10.1097","volume":"61","author":[{"given":"Morven E.","family":"Cunningham","sequence":"first","affiliation":[{"name":"The Liver Unit, Blizard Institute,Queen Mary University of London,London,United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alia","family":"Javaid","sequence":"additional","affiliation":[{"name":"The Liver Unit, Blizard Institute,Queen Mary University of London,London,United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jenny","family":"Waters","sequence":"additional","affiliation":[{"name":"The Liver Unit, Blizard Institute,Queen Mary University of London,London,United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"Davidson\u2010Wright","sequence":"additional","affiliation":[{"name":"The Liver Unit, Blizard Institute,Queen Mary University of London,London,United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joshua L.C.","family":"Wong","sequence":"additional","affiliation":[{"name":"The Liver Unit, Blizard Institute,Queen Mary University of London,London,United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meleri","family":"Jones","sequence":"additional","affiliation":[{"name":"The Liver Unit, Blizard Institute,Queen Mary University of London,London,United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graham R.","family":"Foster","sequence":"additional","affiliation":[{"name":"The Liver Unit, Blizard Institute,Queen Mary University of London,London,United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","published-online":{"date-parts":[[2015,2,13]]},"reference":[{"key":"hep27570-bib-0001-20241017","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1038\/nri3463","article-title":"25 years of interferon\u2010based treatment of chronic hepatitis C: an epoch coming to an end","volume":"13","year":"2013","journal-title":"Nat Rev Immunol"},{"key":"hep27570-bib-0002-20241017","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1056\/NEJMoa1213557","article-title":"Faldaprevir and deleobuvir for HCV genotype 1 infection","volume":"369","year":"2013","journal-title":"N Engl J 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