title: 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.affiliation: Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Shimakami
authors.affiliation: Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Honda
authors.affiliation: Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Shirasaki
authors.affiliation: Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Riuta
authors.initials: R
authors.lastname: Takabatake
authors.affiliation: Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Fanwei
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Murai
authors.affiliation: Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Shiomoto
authors.affiliation: Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Funaki
authors.affiliation: Lineberger Comprehensive Cancer Center and the Division of Infectious Diseases, Department of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7292, USA.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yamane
authors.affiliation: Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Seishi
authors.initials: S
authors.lastname: Murakami
authors.affiliation: Lineberger Comprehensive Cancer Center and the Division of Infectious Diseases, Department of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7292, USA.
authors.forename: Stanley M
authors.initials: SM
authors.lastname: Lemon
authors.affiliation: Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kaneko
mesh_terms: D016588:Anticarcinogenic Agents / Q000494:pharmacology; D000998:Antiviral Agents; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000517:prevention & control / Q000821:virology; D016174:Hepacivirus / Q000254:growth & development*; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000096:biosynthesis; D050356:Lipid Metabolism / Q000187:drug effects; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000517:prevention & control / Q000821:virology; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control; D010441:Peptide Chain Elongation, Translational / Q000187:drug effects; D012367:RNA, Viral / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000096:biosynthesis; D012176:Retinoids / Q000494:pharmacology*; D050794:STAT1 Transcription Factor / Q000096:biosynthesis; D051780:Sterol Regulatory Element Binding Protein 1 / Q000096:biosynthesis; D019065:Virus Assembly / Q000187:drug effects; D057074:Virus Release / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
chemical_list: D016588:Anticarcinogenic Agents; D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D012176:Retinoids; C497387:SREBF1 protein, human; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; C487689:(2E,4E,6E,10E)-3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid
references.citation: Hepatology. 2013 Mar;57(3):925-33
references.pmid: 23213086
references.citation: Cancer Res. 2002 Jul 15;62(14):3997-4006
references.pmid: 12124333
references.citation: Hepatology. 2008 Nov;48(5):1396-403
references.pmid: 18830996
references.citation: J Virol. 2007 Aug;81(15):8122-30
references.pmid: 17507484
references.citation: N Engl J Med. 1999 Apr 1;340(13):1046-7
references.pmid: 10189289
references.citation: J Virol. 2013 May;87(9):5270-86
references.pmid: 23449803
references.citation: BMC Cancer. 2013 Apr 15;13:191
references.pmid: 23587162
references.citation: Hepatol Res. 2010 Sep;40(9):923-9
references.pmid: 20887597
references.citation: Liver Int. 2008 Mar;28(3):347-54
references.pmid: 18290777
references.citation: J Virol. 2013 May;87(9):4994-5004
references.pmid: 23427160
references.citation: Semin Immunopathol. 2013 Jan;35(1):87-100
references.pmid: 23111699
references.citation: N Engl J Med. 2002 Sep 26;347(13):975-82
references.pmid: 12324553
references.citation: PLoS Pathog. 2013;9(4):e1003302
references.pmid: 23593007
references.citation: PLoS Pathog. 2012 Jan;8(1):e1002466
references.pmid: 22241992
references.citation: Transpl Int. 2011 Jan;24(1):43-50
references.pmid: 20649944
references.citation: Gastroenterology. 2005 Feb;128(2):449-62
references.pmid: 15685555
references.citation: J Virol. 2010 Nov;84(22):12048-57
references.pmid: 20826689
references.citation: Cancer Res. 2012 Sep 1;72(17):4459-71
references.pmid: 22651928
references.citation: Biochem Biophys Res Commun. 1995 Feb 6;207(1):382-8
references.pmid: 7857292
references.citation: J Biol Chem. 2009 Nov 27;284(48):33466-74
references.pmid: 19808675
references.citation: J Biol Chem. 2005 Mar 11;280(10):8831-41
references.pmid: 15623509
references.citation: J Hepatol. 2013 Jun;58(6):1081-8
references.pmid: 23354285
references.citation: Gastroenterology. 2011 Feb;140(2):667-75
references.pmid: 21056040
references.citation: J Virol. 2007 Jan;81(2):629-38
references.pmid: 17079282
references.citation: Proc Natl Acad Sci U S A. 2012 Jan 17;109(3):941-6
references.pmid: 22215596
references.citation: N Engl J Med. 1996 Jun 13;334(24):1561-7
references.pmid: 8628336
references.citation: Cancer Prev Res (Phila). 2011 Jan;4(1):128-36
references.pmid: 21071580
references.citation: J Virol. 2009 Sep;83(17):8379-95
references.pmid: 19515772
references.citation: Hepatology. 1999 Jul;30(1):316-24
references.pmid: 10385673
references.citation: World J Gastroenterol. 2011 Dec 21;17(47):5184-90
references.pmid: 22215943
references.citation: Hepatology. 2011 Dec;54(6):1936-46
references.pmid: 21858850
references.citation: J Lab Clin Med. 2003 Jan;141(1):58-66
references.pmid: 12518169
references.citation: Nat Cell Biol. 2007 Sep;9(9):1089-97
references.pmid: 17721513
references.citation: J Biol Chem. 2012 Jan 20;287(4):2280-7
references.pmid: 22090026
references.citation: J Infect Dis. 2010 Jul 1;202(1):75-85
references.pmid: 20497049
references.citation: RNA Biol. 2011 Mar-Apr;8(2):258-69
references.pmid: 21593584
references.citation: J Virol. 2008 Aug;82(16):7964-76
references.pmid: 18524832
references.citation: Antimicrob Agents Chemother. 2007 Jun;51(6):2016-27
references.pmid: 17420205
references.citation: Nat Rev Gastroenterol Hepatol. 2013 May;10(5):268-76
references.pmid: 23419289
references.citation: Curr Opin Virol. 2011 Jul;1(1):19-26
references.pmid: 22440563
references.citation: Nat Med. 2005 Jul;11(7):791-6
references.pmid: 15951748
references.citation: Cell Biol Int. 2006 Dec;30(12):992-8
references.pmid: 16962796
references.citation: J Natl Cancer Inst. 1984 Dec;73(6):1389-93
references.pmid: 6439933