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Apolipoprotein B-dependent hepatitis C virus secretion is inhibited by the grapefruit flavonoid naringenin

Yaakov Nahmias1, Jonathan Goldwasser, Monica Casali

  • 1Center for Engineering in Medicine, Shriners Burns Hospital, Boston, MA, USA. ynahmias@partners.org

Hepatology (Baltimore, Md.)
|April 9, 2008
PubMed

Insights

The grapefruit flavonoid naringenin significantly reduces Hepatitis C virus (HCV) secretion by inhibiting very low density lipoprotein (vLDL) assembly and release. This offers a promising new therapeutic strategy for treating chronic liver disease caused by HCV infection.

Area of Science:

  • Hepatology
  • Virology
  • Biochemistry

Background:

  • Hepatitis C virus (HCV) is a major global cause of chronic liver disease.
  • HCV interacts with host lipid metabolism and lipoproteins for its lifecycle.
  • The mechanism of HCV secretion involves association with very low density lipoprotein (vLDL).

Purpose of the Study:

  • To investigate the role of very low density lipoprotein (vLDL) in Hepatitis C virus (HCV) secretion.
  • To evaluate the potential of naringenin, a grapefruit flavonoid, as an antiviral agent against HCV.

Main Methods:

  • Investigated HCV secretion via a Golgi-dependent mechanism linked to vLDL.
  • Utilized apolipoprotein B (ApoB) messenger RNA silencing to assess its impact on HCV secretion.
  • Examined the effect of naringenin on vLDL secretion, microsomal triglyceride transfer protein (MTP) activity, and key lipid-related gene transcription in HCV-infected cells.

Main Results:

  • Silencing ApoB reduced secretion of both ApoB-100 and HCV by 70%.
  • Naringenin inhibited MTP activity and the transcription of HMGCR and ACAT2.
  • Naringenin treatment decreased HCV secretion by 80% at non-toxic concentrations in hepatocytes and mice.

Conclusions:

  • HCV is secreted via a vLDL-dependent pathway.
  • Naringenin effectively inhibits HCV secretion by targeting lipid metabolism pathways.
  • Naringenin represents a potential novel therapeutic for Hepatitis C virus infection.
Abstract

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