BST-2 Expression in Human Hepatocytes is Inducible by All Three Types of Interferons and Restricts Production of Hepatitis C Virus

ISSN: 1875-5666 (Online)
ISSN: 1566-5240 (Print)

Volume 17, 10 Issues, 2017

Download PDF Flyer

Current Molecular Medicine

This journal supports open access

Aims & ScopeAbstracted/Indexed in

Ranking and Category:
  • 47th of 124 in Medicine, Research & Experimental

Submit Abstracts Online Submit Manuscripts Online

David W. Li
College of Medicine
University of Nebraska Medical Center
Omaha, NE

View Full Editorial Board

Subscribe Purchase Articles Order Reprints

Current: 2.912
5 - Year: 3.478

BST-2 Expression in Human Hepatocytes is Inducible by All Three Types of Interferons and Restricts Production of Hepatitis C Virus

Current Molecular Medicine, 14(3): 349-360.

Author(s): T. Amet, D. Byrd, N. Hu, Q. Sun, F. Li, Y. Zhao, S. Hu, A. Grantham and Q Yu.

Affiliation: Department of Microbiology and Immunology and Center for AIDS Research, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, IN 46202, USA.


Bone marrow stromal cell antigen 2 (BST-2, also known as tetherin, CD317, or HM1.24) has recently been identified as a host restriction factor against diverse families of enveloped viruses. However, the effects of BST-2 on the life cycle of hepatitis C virus (HCV), an enveloped RNA virus, remain unclear and controversial. Here we demonstrated that human hepatocytes including Huh7.5.1 cells, primary human hepatocytes (PHHs), and HepG2 cells constitutively expressed low to moderate levels of endogenous BST-2 on the cell surface, which could be robustly up-regulated by all three types of interferons (IFNs) such as IFN-α, IFN-γ, and IFN-λ. IFN-α and IFN-γ showed a synergistic effect in induction of BST-2 expression on human hepatocytes. Over-expression of BST-2 by BST-2-expressing vector transfection or up-regulation of BST-2 by IFN stimulation markedly suppressed HCV production, whereas shRNA-mediated depletion of endogenous BST-2 significantly enhanced HCV production in infected Huh7.5.1 cells. IFN-mediated anti-HCV activity was partially but significantly diminished by shRNA-mediated knockdown of BST-2 expression, indicating that BST- 2 upregulation is directly involved in IFN-mediated inhibition of HCV production. We also found that both BST-2 and HCV core co-localized with intracellular lipid droplets (LDs), suggesting that BST-2-HCV interaction may take place around LDs as LDs constitute an important intracellular organelle for HCV assembly and replication. Taken together, our data suggest that BST-2 is a host restriction factor against HCV, and induction of BST-2 in hepatocytes could be one of the mechanisms by which current HCV standard therapy (IFN-α plus ribavirin) achieves a sustained virological response (SVR).


BST-2, HCV, host restriction factor, Huh7.5.1 cell, interferon, lipid droplet.

Purchase Online Order Reprints Order Eprints Rights and Permissions

Article Details

Volume: 14
Issue Number: 3
First Page: 349
Last Page: 360
Page Count: 12
DOI: 10.2174/1566524013666131118111719
Price: $58

Related Journals

Webmaster Contact: Copyright © 2016 Bentham Science