The acyclic retinoid Peretinoin inhibits hepatitis C virus replication and infectious virus release in vitro.

Abstract

Clinical studies suggest that the oral acyclic retinoid Peretinoin may reduce the recurrence of hepatocellular carcinoma (HCC) following surgical ablation of primary tumours. Since hepatitis C virus (HCV) infection is a major cause of HCC, we assessed whether Peretinoin and other retinoids have any effect on HCV infection. For this purpose, we measured the effects of several retinoids on the replication of genotype 1a, 1b, and 2a HCV in vitro. Peretinoin inhibited RNA replication for all genotypes and showed the strongest antiviral effect among the retinoids tested. Furthermore, it reduced infectious virus release by 80-90% without affecting virus assembly. These effects could be due to reduced signalling from lipid droplets, triglyceride abundance, and the expression of mature sterol regulatory element-binding protein 1c and fatty acid synthase. These negative effects of Peretinoin on HCV infection may be beneficial in addition to its potential for HCC chemoprevention in HCV-infected patients.

• Authors: Tetsuro Shimakami, Masao Honda, Takayoshi Shirasaki, Riuta Takabatake, Fanwei Liu, Kazuhisa Murai, Takayuki Shiomoto, Masaya Funaki, Daisuke Yamane, Seishi Murakami, Stanley M Lemon, Shuichi Kaneko
• Journal: Scientific reports (Sci Rep) Vol. 4 Pg. 4688 (Apr 15 2014) ISSN: 2045-2322 [Electronic] England
• PMID: 24732793 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anticarcinogenic Agents
• Antiviral Agents
• Interferon alpha-2
• Interferon-alpha
• RNA, Viral
• Recombinant Proteins
• Retinoids
• SREBF1 protein, human
• STAT1 Transcription Factor
• STAT1 protein, human
• Sterol Regulatory Element Binding Protein 1
• (2E,4E,6E,10E)-3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid

Topics

• Anticarcinogenic Agents (pharmacology)
• Antiviral Agents
• Carcinoma, Hepatocellular (drug therapy, prevention & control, virology)
• Hepacivirus (growth & development)
• Hepatitis C (drug therapy)
• Humans
• Interferon alpha-2
• Interferon-alpha (biosynthesis)
• Lipid Metabolism (drug effects)
• Liver Neoplasms (drug therapy, prevention & control, virology)
• Neoplasm Recurrence, Local (prevention & control)
• Peptide Chain Elongation, Translational (drug effects)
• RNA, Viral (biosynthesis)
• Recombinant Proteins (biosynthesis)
• Retinoids (pharmacology)
• STAT1 Transcription Factor (biosynthesis)
• Sterol Regulatory Element Binding Protein 1 (biosynthesis)
• Virus Assembly (drug effects)
• Virus Release (drug effects)
• Virus Replication (drug effects)