The heat shock protein inhibitor Quercetin attenuates hepatitis C virus production†

• DOI: 10.1002/hep.23232
• Publication Date: 2009-08-11T07:48:52Z
• Authors: Oscar Gonzalez; Vanessa Fontanes; Santanu Raychaudhuri; Rachel Loo; Joseph Loo; Vaithilingaraja A...; Ren Sun; Asim Dasgupta; Samuel W. French
• Keywords: NS5A

The hepatitis C viral (HCV) genome is translated through an internal ribosome entry site (IRES) as a single polyprotein precursor that subsequently cleaved into individual mature proteins. Nonstructural protein 5A (NS5A) one of these proteins has been implicated in regulation replication, translation from the IRES and packaging. We sought to identify cellular interact with NS5A determine whether interactions may play role production. Mass spectrometric analysis coimmunoprecipitated complexes cell extracts identified heat shock (HSPs) 40 70. confirmed NS5A/HSP interaction by confocal microscopy demonstrating colocalization HSP40 HSP70. Western further HSP70 NS5A. A transient transfection, luciferase-based, tissue culture assay demonstrated augmentation HCV IRES-mediated translation, small interfering RNA (siRNA)-mediated knockdown reduced this augmentation. Treatment inhibitor HSP synthesis, Quercetin, markedly baseline activity its also modestly accumulation, whereas both infectious particle production system using J6/JFH virus fused Renilla luciferase reporter. Quercetin at nontoxic concentrations. marked inhibition partially be related reduction their potential involvement well morphogenesis or secretion.Quercetin allow for dissection life cycle therapeutic use reduce low associated toxicity.