Basic Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 7, 2016; 22(45): 9954-9965
Published online Dec 7, 2016. doi: 10.3748/wjg.v22.i45.9954
Apolipoprotein B100 is required for hepatitis C infectivity and Mipomersen inhibits hepatitis C
Esperance A K Schaefer, James Meixiong, Christina Mark, Amy Deik, Daniel L Motola, Dahlene Fusco, Andrew Yang, Cynthia Brisac, Shadi Salloum, Wenyu Lin, Clary B Clish, Lee F Peng, Raymond T Chung
James Meixiong, Christina Mark, Daniel L Motola, Dahlene Fusco, Andrew Yang, Cynthia Brisac, Shadi Salloum, Wenyu Lin, Lee F Peng, Raymond T Chung, Esperance AK Schaefer, Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA 02114, United States
Daniel L Motola, Lee F Peng, Raymond T Chung, Esperance AK Schaefer, Department of Medicine, Harvard Medical School, Boston, MA 02115, United States
Clary B Clish, Amy Deik, both of the Broad Institute of Harvard and M.I.T., Cambridge, MA 02142, United States
Lee F Peng, Temple University Health System, Philadelphia, PA 19140, United States
Author contributions: Schaefer EAK designed and interpreted all experiments and prepared the manuscript; Meixiong J, Mark C, Fusco D, Yang A, Brisac C, Salloum S and Lin W assisted in designing and interpreting entry, replicon and infectivity assays; Meixiong J and Mark C assisted with designing and interpreting experiments involving mipomersen; Motola DL performed TALEN cell line generation and design of experiments; Peng LF and Chung RT designed and interpreted all experiments and prepared the manuscript; Peng LF and Chung RT contributed equally to this manuscript; all the authors contributed to this manuscript.
Supported by the United States National Institutes of Health (NIH), No. F32-DK097855 (to Schaefer EAK), No. T32-DK008191 (to Motola DL), No. K08-DK088951 (to Peng LF), and No. K24-DK078772 (to Chung RT).
Institutional review board statement: No patients or patient-derived samples were involved in this study.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Data sharing statement: Technical appendix and data set available from the corresponding author.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Lee F Peng, Associate Medical Director of Liver Transplantation, Associate Professor of Medicine, Temple University Health System, 3509 N. Broad St., 9th Floor, Philadelphia, PA 19140, United States. lee.peng@tuhs.temple.edu
Telephone: +1-215-7075067 Fax: +1-215-7075124
Received: July 22, 2016
Peer-review started: July 25, 2016
First decision: September 20, 2016
Revised: October 1, 2016
Accepted: October 27, 2016
Article in press: October 27, 2016
Published online: December 7, 2016
Core Tip

Core tip: Hepatitis C virus (HCV) circulates as a very-low-density lipoprotein (VLDL)-like lipoviral particle. Apolipoprotein B100 (apoB100) is the core protein of VLDL, buts its role in HCV has remained incompletely characterized. Use of gene-editing with transcription activator-like effector nucleases permits the characterization of the role of apoB100 in HCV. We demonstrate that apoB100 is required for HCV infection. Loss of apoB100 results in the secretion of HCV virions with an altered lipid composition and limited ability to infect naive cells. Mipomersen, an FDA-approved antisense inhibitor of apoB100, has an anti-HCV effect and limits the viral infectivity.