The sirtuin inhibitor sirtinol inhibits hepatitis A virus (HAV) replication by inhibiting HAV internal ribosomal entry site activity

Biochem Biophys Res Commun. 2015 Oct 23;466(3):567-71. doi: 10.1016/j.bbrc.2015.09.083. Epub 2015 Sep 24.

Abstract

Epigenetics plays a role in the regulation of gene expression. Epigenetic changes control gene expression at the transcriptional level. Our previous study suggested that the La protein, which is mainly localized in the nucleus, was associated with hepatitis A virus (HAV) internal ribosomal entry site (IRES)-mediated translation and HAV replication. The aim of this study was to investigate whether epigenetic compounds have effects on HAV IRES-mediated translation and HAV replication. Sirtinol, a sirtuin inhibitor, inhibited HAV IRES-mediated translation in COS7-HAV-IRES cells. Treatment with 10 μM sirtinol resulted in a significant reduction in the intracellular RNA levels of HAV HA11-1299 genotype IIIA in Huh7 cells. Epigenetic treatment with a sirtuin inhibitor may represent a new treatment option for HAV infection. In conclusion, epigenetic control was involved in HAV IRES-dependent translation and HAV replication. Special attention should also be paid to underlying viral diseases in the clinical use of epigenetic treatments for malignancies.

Keywords: HAV; IRES; JNJ-7706621; Sirtinol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amantadine / pharmacology
  • Animals
  • Antiviral Agents / pharmacology
  • Benzamides / pharmacology*
  • COS Cells
  • Cell Line
  • Chlorocebus aethiops
  • Epigenesis, Genetic / drug effects
  • Hepatitis A virus / drug effects*
  • Hepatitis A virus / genetics
  • Hepatitis A virus / physiology
  • Histone Deacetylase Inhibitors / pharmacology
  • Host-Pathogen Interactions
  • Humans
  • Internal Ribosome Entry Sites / drug effects*
  • Internal Ribosome Entry Sites / genetics
  • Naphthols / pharmacology*
  • Phosphoproteins / metabolism
  • Protein Biosynthesis / drug effects
  • RNA, Viral / genetics
  • RNA, Viral / metabolism
  • Sirtuins / antagonists & inhibitors*
  • Triazoles / pharmacology
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Benzamides
  • Histone Deacetylase Inhibitors
  • Internal Ribosome Entry Sites
  • JNJ-7706621
  • La protein, human
  • Naphthols
  • Phosphoproteins
  • RNA, Viral
  • Triazoles
  • sirtinol
  • Amantadine
  • Sirtuins