BST-2 expression in human hepatocytes is inducible by all three types of interferons and restricts production of hepatitis C virus

T. Amet, D. Byrd, N. Hu, Q. Sun, F. Li, Y. Zhao, S. Hu, A. Grantham, Q. Yu

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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).

Original languageEnglish (US)
Pages (from-to)349-360
Number of pages12
JournalCurrent Molecular Medicine
Volume14
Issue number3
DOIs
StatePublished - Jan 1 2014

Fingerprint

Viruses
Hepacivirus
Interferons
Hepatocytes
Small Interfering RNA
Lipids
Up-Regulation
Virus Assembly
Virus Activation
Ribavirin
RNA Viruses
Hep G2 Cells
Virus Replication
Life Cycle Stages
Mesenchymal Stromal Cells
Organelles
Transfection
Life cycle
Bone
Antigens

Keywords

  • BST-2
  • HCV
  • Host restriction factor
  • Huh7.5.1 cell
  • Interferon
  • Lipid droplet

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Molecular Medicine

Cite this

BST-2 expression in human hepatocytes is inducible by all three types of interferons and restricts production of hepatitis C virus. / Amet, T.; Byrd, D.; Hu, N.; Sun, Q.; Li, F.; Zhao, Y.; Hu, S.; Grantham, A.; Yu, Q.

In: Current Molecular Medicine, Vol. 14, No. 3, 01.01.2014, p. 349-360.

Research output: Contribution to journalArticle

Amet, T. ; Byrd, D. ; Hu, N. ; Sun, Q. ; Li, F. ; Zhao, Y. ; Hu, S. ; Grantham, A. ; Yu, Q. / BST-2 expression in human hepatocytes is inducible by all three types of interferons and restricts production of hepatitis C virus. In: Current Molecular Medicine. 2014 ; Vol. 14, No. 3. pp. 349-360.
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