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New advances in the molecular biology of hepatitis C virus infection: towards the identification of new treatment targets
  1. Alexander Ploss1,
  2. Jean Dubuisson2
  1. 1Center for the Study of Hepatitis C, Laboratory for Virology and Infectious Diseases, The Rockefeller University, New York, USA
  2. 2Molecular and Cellular Virology of Hepatitis C, Center for Infection and Immunity of Lille (CIIL), Université Lille Nord de France, Institut Pasteur de Lille, Lille, France
  1. Correspondence to Professor Alexander Ploss, The Rockefeller University, Center for the Study of Hepatitis C, Laboratory for Virology and Infectious Diseases, 1230 York Avenue, Box 64, New York 10065, USA; aploss{at}rockefeller.edu Professor Jean Dubuisson, Molecular & Cellular Virology of Hepatitis C, Center for Infection & Immunity of Lille (CIIL), Universite Lille Nord de France,Institut Pasteur de Lille, Lille, France; jean.dubuisson{at}ibl.fr

Abstract

Hepatitis C virus (HCV) causes chronic infection in almost 2% of the world's population. If untreated, chronic carriers can develop severe liver disease including fibrosis, cirrhosis and hepatocellular carcinoma. Until recently, hepatitis C was treated with a combination of pegylated interferon and ribavirin, a treatment which was only partially effective and was plagued with side effects. In 2011 two inhibitors of the virally encoded NS3/4 protease have become part of standard therapy, which have improved treatment rates but can exacerbate the problematic side effects. While the addition of these first directly acting antivirals (DAAs) marks a milestone in anti-HCV therapy, new and improved combinations of drugs are desperately needed. New generations of drugs will have to address genetic variability of HCV and issues of viral resistance. Furthermore, combination therapies have to be tailored to effectively cure patient populations that have traditionally been hardest to treat, including patients with cirrhosis, those receiving liver transplants and individuals who are co-infected with HIV or hepatitis B virus. Since the discovery of HCV a plethora of experimental tools have been developed which enabled detailed analysis of various aspects of the viral life cycle and the interaction of HCV with its human host. Such studies have revealed a growing list of targets for therapeutic intervention, some of which will be discussed in this review.

  • Hepatitis C virus
  • viral hepatitis
  • drug targets
  • liver disease
  • infectious diseases
  • HCV
  • hepatitis C

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Footnotes

  • Funding This work was supported in part by award number RC1DK087193 (AP) from the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases, Infectious Disease Society of America Astella Young Investigator Award (AP) and the French ‘Agence Nationale de Recherche sur le Sida et les hépatites virales’ (ANRS) (JD).

  • Competing interests None.

  • Provenance and peer review Commissioned; externally peer reviewed.

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