{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T16:43:25Z","timestamp":1790613805711,"version":"4.1.0"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2017,4,28]],"date-time":"2017-04-28T00:00:00Z","timestamp":1493337600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2017,6]]},"abstract":"<jats:p>\n                    The development of different cell culture models has greatly contributed to increased understanding of the hepatitis C virus (HCV) life cycle. However, it is still challenging to grow HCV clinical isolates in cell culture. If overcome, this would open new perspectives to study HCV biology, including drug\u2010resistant variants emerging with new antiviral therapies. In this study we hypothesized that this hurdle could be due to the presence of inhibitory factors in patient serum. Combining polyethylene glycol precipitation, iodixanol gradient, and size\u2010exclusion chromatography, we obtained from HCV\u2010seronegative sera a purified fraction enriched in inhibitory factors. Mass spectrometric analysis identified apolipoprotein(a) (apo[a]) as a potential inhibitor of HCV entry. Apo(a) consists of 10 kringle IV domains (KIVs), one kringle V domain, and an inactive protease domain. The 10 KIVs are present in a single copy with the exception of KIV type 2 (KIV\n                    <jats:sub>2<\/jats:sub>\n                    ), which is encoded in a variable number of tandemly repeated copies, giving rise to numerous apo(a) size isoforms. In addition, apo(a) covalently links to the apolipoprotein B component of a low\u2010density lipoprotein through a disulfide bridge to form lipoprotein(a). Using a recombinant virus derived from the JFH1 strain, we confirmed that plasma\u2010derived and recombinant lipoprotein(a) as well as purified recombinant apo(a) variants were able to specifically inhibit HCV by interacting with infectious particles. Our results also suggest that small isoforms are less inhibitory than the large ones. Finally, we observed that the lipoprotein moiety of HCV lipoviroparticles was essential for inhibition, whereas functional lysine\u2010binding sites in KIV\n                    <jats:sub>7<\/jats:sub>\n                    , KIV\n                    <jats:sub>8<\/jats:sub>\n                    , and KIV\n                    <jats:sub>10<\/jats:sub>\n                    were not required.\n                    <jats:italic toggle=\"yes\">Conclusions<\/jats:italic>\n                    : Our results identify apo(a) as an additional component of the lipid metabolism modulating HCV infection. (H\n                    <jats:sc>epatology<\/jats:sc>\n                    2017;65:1851\u20101864)\n                  <\/jats:p>","DOI":"10.1002\/hep.29096","type":"journal-article","created":{"date-parts":[[2017,2,2]],"date-time":"2017-02-02T17:59:36Z","timestamp":1486058376000},"page":"1851-1864","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":16,"title":["Apolipoprotein(a) inhibits hepatitis C virus entry through interaction with infectious particles"],"prefix":"10.1097","volume":"65","author":[{"given":"Catarina","family":"Oliveira","sequence":"first","affiliation":[{"name":"EA4294, Laboratoire de Virologie, Centre Universitaire de Recherche en Sant\u00e9, Centre Hospitalier Universitaire et Universit\u00e9 de Picardie Jules Verne,Amiens,France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carole","family":"Fournier","sequence":"additional","affiliation":[{"name":"EA4294, Laboratoire de Virologie, Centre Universitaire de Recherche en Sant\u00e9, Centre Hospitalier Universitaire et Universit\u00e9 de Picardie Jules Verne,Amiens,France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique","family":"Descamps","sequence":"additional","affiliation":[{"name":"EA4294, Laboratoire de Virologie, Centre Universitaire de Recherche en Sant\u00e9, Centre Hospitalier Universitaire et Universit\u00e9 de Picardie Jules Verne,Amiens,France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginie","family":"Morel","sequence":"additional","affiliation":[{"name":"EA4294, Laboratoire de Virologie, Centre Universitaire de Recherche en Sant\u00e9, Centre Hospitalier Universitaire et Universit\u00e9 de Picardie Jules Verne,Amiens,France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corey A.","family":"Scipione","sequence":"additional","affiliation":[{"name":"Robarts Research Institute, Schulich School of Medicine & Dentistry,Western University,London,ON,Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rocco","family":"Romagnuolo","sequence":"additional","affiliation":[{"name":"Department of Chemistry & Biochemistry,University of Windsor,Windsor,ON,Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlys L.","family":"Koschinsky","sequence":"additional","affiliation":[{"name":"Robarts Research Institute, Schulich School of Medicine & Dentistry,Western University,London,ON,Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agn\u00e8s","family":"Boullier","sequence":"additional","affiliation":[{"name":"INSERM U1088, Centre Universitaire de Recherche en Sant\u00e9, Centre Hospitalier Universitaire et Universit\u00e9 de Picardie Jules Verne,Amiens,France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo","family":"Marcelo","sequence":"additional","affiliation":[{"name":"Plateforme ICAP, Centre Universitaire de Recherche en Sant\u00e9, Universit\u00e9 de Picardie Jules Verne,Amiens,France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Marc","family":"Domon","sequence":"additional","affiliation":[{"name":"EA3900 BIOPI, Biologie des Plantes et Innovation, UFR des Sciences, Universit\u00e9 de Picardie Jules Verne,Amiens,France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etienne","family":"Brochot","sequence":"additional","affiliation":[{"name":"EA4294, Laboratoire de Virologie, Centre Universitaire de Recherche en Sant\u00e9, Centre Hospitalier Universitaire et Universit\u00e9 de Picardie Jules Verne,Amiens,France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles","family":"Duverlie","sequence":"additional","affiliation":[{"name":"EA4294, Laboratoire de Virologie, Centre Universitaire de Recherche en Sant\u00e9, Centre Hospitalier Universitaire et Universit\u00e9 de Picardie Jules Verne,Amiens,France"},{"name":"Biobanque de Picardie, Centre Hospitalier Universitaire,Amiens,France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Francois","sequence":"additional","affiliation":[{"name":"EA4294, Laboratoire de Virologie, Centre Universitaire de Recherche en Sant\u00e9, Centre Hospitalier Universitaire et Universit\u00e9 de Picardie Jules Verne,Amiens,France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Castelain","sequence":"additional","affiliation":[{"name":"EA4294, Laboratoire de Virologie, Centre Universitaire de Recherche en Sant\u00e9, Centre Hospitalier Universitaire et Universit\u00e9 de Picardie Jules Verne,Amiens,France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6884-2456","authenticated-orcid":false,"given":"Francois","family":"Helle","sequence":"additional","affiliation":[{"name":"EA4294, Laboratoire de Virologie, Centre Universitaire de Recherche en Sant\u00e9, Centre 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