title: Targeting ribosome assembly on the HCV RNA using a small RNA molecule.
abstract: Translation initiation of hepatitis C Virus (HCV) RNA is the initial obligatory step of the viral life cycle, mediated through the Internal Ribosome Entry Site (IRES) present in the 5'-untranslated region (UTR). Initiation on the HCV IRES is mediated by multiple structure-specific interactions between IRES RNA and host 40S ribosomal subunit. In the present study we demonstrate that the SLIIIef domain, in isolation from other structural elements of HCV IRES, retain the ability to interact with 40S ribosome subunit. A small RNA SLRef, mimicking the SLIIIef domain was found to interact specifically with human La protein and the ribosomal protein S5 and selectively inhibit HCV RNA translation. More importantly, SLRef RNA showed significant suppression of replication in HCV monocistronic replicon and decrease of negative strand synthesis in HCV cell culture system. Finally, using Sendai virus based virosome, the targeted delivery of SLRef RNA into mice liver succeeded in selectively inhibiting HCV IRES mediated translation in vivo.
authors.affiliation: Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India.
authors.forename: Prasanna
authors.initials: P
authors.lastname: Bhat
authors.forename: Sivakumar Vadivel
authors.initials: SV
authors.lastname: Gnanasundram
authors.forename: Prashant
authors.initials: P
authors.lastname: Mani
authors.forename: Partho Sarothi
authors.initials: PS
authors.lastname: Ray
authors.forename: Debi P
authors.initials: DP
authors.lastname: Sarkar
authors.forename: Saumitra
authors.initials: S
authors.lastname: Das
mesh_terms: D000818:Animals; D001483:Base Sequence; D005260:Female; D016174:Hepacivirus / Q000235:genetics* / Q000378:metabolism; D008099:Liver; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010442:Peptide Chain Initiation, Translational / Q000187:drug effects*; D058727:RNA, Small Untranslated / Q000737:chemistry / Q000494:pharmacology*; D012367:RNA, Viral / Q000378:metabolism*; D054682:Ribosome Subunits, Small, Eukaryotic / Q000378:metabolism*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D058727:RNA, Small Untranslated; D012367:RNA, Viral