title: Inhibition of hepatitis C virus production by aptamers against the core protein.
abstract: Hepatitis C virus (HCV) core protein is essential for virus assembly. HCV core protein was expressed and purified. Aptamers against core protein were raised through the selective evolution of ligands by the exponential enrichment approach. Detection of HCV infection by core aptamers and the antiviral activities of aptamers were characterized. The mechanism of their anti-HCV activity was determined. The data showed that selected aptamers against core specifically recognize the recombinant core protein but also can detect serum samples from hepatitis C patients. Aptamers have no effect on HCV RNA replication in the infectious cell culture system. However, the aptamers inhibit the production of infectious virus particles. Beta interferon (IFN-β) and interferon-stimulated genes (ISGs) are not induced in virally infected hepatocytes by aptamers. Domains I and II of core protein are involved in the inhibition of infectious virus production by the aptamers. V31A within core is the major resistance mutation identified. Further study shows that the aptamers disrupt the localization of core with lipid droplets and NS5A and perturb the association of core protein with viral RNA. The data suggest that aptamers against HCV core protein inhibit infectious virus production by disrupting the localization of core with lipid droplets and NS5A and preventing the association of core protein with viral RNA. The aptamers for core protein may be used to understand the mechanisms of virus assembly. Core-specific aptamers may hold promise for development as early diagnostic reagents and potential therapeutic agents for chronic hepatitis C.
authors.affiliation: Department of Molecular Medicine, State Key Laboratory of Chemo/Biosensing and Chemometrics, Hunan University, Changsha, China.
authors.forename: Shali
authors.initials: S
authors.lastname: Shi
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Yu
authors.forename: Yimin
authors.initials: Y
authors.lastname: Gao
authors.forename: Binbin
authors.initials: B
authors.lastname: Xue
authors.forename: Xinjiao
authors.initials: X
authors.lastname: Wu
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Wang
authors.forename: Darong
authors.initials: D
authors.lastname: Yang
authors.forename: Haizhen
authors.initials: H
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D052157:Aptamers, Nucleotide / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D015153:Blotting, Western; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D015723:Gene Library; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D010957:Plasmids / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D060888:Real-Time Polymerase Chain Reaction; D052156:SELEX Aptamer Technique; D014758:Viral Core Proteins / Q000235:genetics / Q000378:metabolism*; D014771:Virion / Q000187:drug effects*
chemical_list: D000911:Antibodies, Monoclonal; D052157:Aptamers, Nucleotide; D017931:DNA Primers; D014758:Viral Core Proteins