Suppression of hepatitis A virus genome translation and replication by siRNAs targeting the internal ribosomal entry site

Biochem Biophys Res Commun. 2005 May 20;330(4):1217-23. doi: 10.1016/j.bbrc.2005.03.105.


Small interfering RNAs (siRNAs) targeting the coding region of hepatitis A virus (HAV) were shown to specifically inhibit viral genome replication. Compared to the coding region, the HAV internal ribosomal entry site (IRES) in the 5' non-coding region is highly sequence-conserved and folds into stable secondary structures. Here, we report efficient and sustained RNA interference mediated by both RNase III-prepared siRNA (esiRNA) and vector-derived short hairpin RNAs (shRNAs) that are targeted to various domains of the HAV IRES. Using reporter constructs, and the DNA-based HAV replicon system, we found that shRNAs targeting the HAV IRES domains IIIc and V sustainably suppressed genome translation and replication whereas the IRES domains IIIa and IV were resistant to RNA interference. Our study suggests that some HAV IRES domains might be used as a universal and effective target for specific inhibition of HAV infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Genetic Vectors
  • Genome, Viral
  • Hepatitis A virus / drug effects*
  • Hepatitis A virus / genetics
  • Hepatitis A virus / physiology
  • Molecular Sequence Data
  • Nucleic Acid Conformation
  • Protein Biosynthesis / drug effects
  • RNA, Small Interfering / chemical synthesis
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / pharmacology*
  • RNA, Viral / genetics
  • Ribonuclease III / chemistry
  • Ribosomes / genetics
  • Viral Proteins / biosynthesis
  • Viral Proteins / genetics
  • Virus Replication / drug effects
  • Virus Replication / genetics


  • RNA, Small Interfering
  • RNA, Viral
  • Viral Proteins
  • Ribonuclease III