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Chapter I. Overview on the Properties and Functions of the Core Protein of Hepatitis C Virus (HCV), pp. 1-47 $100.00
Authors:  (Roland Ivanyi-Nagy, Zuzanna Makowska, Marcelo Lopez Lastra, Jean-Luc Darlix, Molecular Parasitology Group, The Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom, and others)
The hepatitis C virus (HCV) core protein is a small, highly basic RNA-binding protein that presumably coats and protects the viral genomic RNA, forming the virion nucleocapsid. Core protein specifically associates with the structured 5‟ and 3‟ untranslated regions (UTRs) of the viral genome and, due to its RNA chaperone activity, induces essential structural rearrangements in the target RNA. Binding to the 5‟ UTR regulates viral polyprotein synthesis, while chaperoning the 3‟ UTR may influence genome replication and possibly genetic variability. Recent results show that HCV and other flavivirus core proteins belong to the class of intrinsically unstructured proteins (IUPs). Due to its inherent flexibility, core protein participates in a variety of specific/weak affinity protein-protein interactions with cellular targets, thereby possibly exerting an influence on a number of vital processes, including regulation of cellular transcription, apoptosis, signaling and immunomodulation. As a result, core has been ascribed to play a major role in HCV infection-associated pathologies, such as hepatic steatosis, type 2 diabetes and malignant transformation leading to hepatocellular carcinoma, but this is still controversial. Lack of an efficient model system for HCV virion production had for a long time precluded direct characterization of core protein function in virus assembly and budding. The recent development of a cell culture system supporting the complete HCV replicative cycle created conditions for an improved understanding of HCV biology. As a highly expressed and conserved viral antigen, core protein is ideally suited to occupy a central role in future treatment possibilities, either for vaccination or as a small molecule drug target. In this chapter we describe the current status of knowledge about the multifunctional role of HCV core protein in virion structure, viral replication and virus-host cell interactions that might be central to pathogenesis during persistent HCV infection. Furthermore, we examine the reasons for the lack of anti-core protein drug candidates in the RandD pipeline and argue that efforts in this direction should be of high priority. 

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Chapter I. Overview on the Properties and Functions of the Core Protein of Hepatitis C Virus (HCV), pp. 1-47