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Intriguing structure of the HCV particle
  1. Agata Budkowska
  1. Correspondence to Dr Agata Budkowska, Scientific Advisor for the Department of International Affairs, Institut Pasteur, 25/28 Rue du Dr Roux, Paris 75724, France; agata.budkowska{at}pasteur.fr

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HCV is a major cause of chronic liver disease worldwide. Much has been learned about HCV since its discovery 27 years ago by molecular cloning when standard virological methods failed to identify this important human pathogen. Elaboration of in vitro models enabled studies of the HCV life cycle and a search for inhibitors of viral replication, leading to the development of effective therapies of chronic HCV infection based on direct-acting antivirals with cure rates of more than 95%.

Despite of the tremendous success of HCV therapy and substantial progress in our knowledge of the virus life cycle, the structure, composition and morphogenesis of HCV particles circulating in the blood of infected patients still remain elusive and determination of the ultrastructure of HCV particles by electron microscopy is a significant challenge.

The putative infectious HCV particle consists of a nucleocapsid-containing the single-stranded RNA genome associated with the viral core protein and a lipid bilayer where the viral envelope proteins (E1 and E2) are assembled as heterodimers. In reality, the structure of HCV is more complex and the virus exhibits unusual and striking features. Indeed, a hallmark of HCV particles is their association with host-cell lipids and lipoproteins, mainly very low-density lipoproteins (VLDL) and low-density lipoproteins (LDL).1 ,2 Thus, virus particles in patients' sera …

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