Apolipoprotein(a) inhibits hepatitis C virus entry through interaction with infectious particles

• DOI: 10.1002/hep.29096
• Publication Date: 2017-02-02T22:59:36Z
• Authors: Catarina Oliveira; Carole Fournier; Véronique Descamps; Virginie Morel; Corey A. Scipione; Rocco Romagnuolo; Marlys L. Koschinsky; Agnès Boullier; Paulo Marcelo; Jean‐Marc Domon; Etienne Brochot; Gilles Duverlie; Catherine Francois; Sandrine Castelain; Francois Helle
• Keywords: NS2-3 protease

The development of different cell culture models has greatly contributed to increased understanding the hepatitis C virus (HCV) life cycle. However, it is still challenging grow HCV clinical isolates in culture. If overcome, this would open new perspectives study biology, including drug‐resistant variants emerging with antiviral therapies. In we hypothesized that hurdle could be due presence inhibitory factors patient serum. Combining polyethylene glycol precipitation, iodixanol gradient, and size‐exclusion chromatography, obtained from HCV‐seronegative sera a purified fraction enriched factors. Mass spectrometric analysis identified apolipoprotein(a) (apo[a]) as potential inhibitor entry. Apo(a) consists 10 kringle IV domains (KIVs), one V domain, an inactive protease domain. KIVs are present single copy exception KIV type 2 (KIV ), which encoded variable number tandemly repeated copies, giving rise numerous apo(a) size isoforms. addition, covalently links apolipoprotein B component low‐density lipoprotein through disulfide bridge form lipoprotein(a). Using recombinant derived JFH1 strain, confirmed plasma‐derived lipoprotein(a) well were able specifically inhibit by interacting infectious particles. Our results also suggest small isoforms less than large ones. Finally, observed moiety lipoviroparticles was essential for inhibition, whereas functional lysine‐binding sites 7 , 8 not required. Conclusions : identify additional lipid metabolism modulating infection. (H epatology 2017;65:1851‐1864)