title: Suppression of hepatitis A virus genome translation and replication by siRNAs targeting the internal ribosomal entry site.
abstract: 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.
authors.affiliation: Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8677, Japan.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kanda
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.forename: Yuri
authors.initials: Y
authors.lastname: Kusov
authors.forename: Osamu
authors.initials: O
authors.lastname: Yokosuka
authors.forename: Verena
authors.initials: V
authors.lastname: Gauss-Müller
mesh_terms: D001483:Base Sequence; D005822:Genetic Vectors; D016679:Genome, Viral; D030041:Hepatitis A virus / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D014176:Protein Biosynthesis / Q000187:drug effects; D034741:RNA, Small Interfering / Q000138:chemical synthesis / Q000235:genetics / Q000494:pharmacology*; D012367:RNA, Viral / Q000235:genetics; D043244:Ribonuclease III / Q000737:chemistry; D012270:Ribosomes / Q000235:genetics; D014764:Viral Proteins / Q000096:biosynthesis / Q000235:genetics; D014779:Virus Replication / Q000187:drug effects / Q000235:genetics
chemical_list: D034741:RNA, Small Interfering; D012367:RNA, Viral; D014764:Viral Proteins; D043244:Ribonuclease III