Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Apr 28, 2015; 7(6): 831-845
Published online Apr 28, 2015. doi: 10.4254/wjh.v7.i6.831
Hepatitis C virus genetic variability and evolution
Natalia Echeverría, Gonzalo Moratorio, Juan Cristina, Pilar Moreno
Natalia Echeverría, Gonzalo Moratorio, Juan Cristina, Pilar Moreno, Laboratorio de Virología Molecular, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, 11400 Montevideo, Uruguay
Gonzalo Moratorio, Viral Populations and Pathogenesis Laboratory, Institut Pasteur, 75724 Paris CEDEX 15, France
Pilar Moreno, Recombinant Proteins Unit, Institut Pasteur de Montevideo, 11400 Montevideo, Uruguay
Author contributions: Echeverría N contributed to bibliographical revision, figures and table design and article drafting; Moratorio G made contributions to bibliographical revision, table design, article drafting and revision; Cristina J contributed to article drafting and critically revised the manuscript for intellectual content; Moreno P made substantial contributions to conception and design, article drafting and revision of intellectual content; all authors contributed to final approval of the version to be published.
Supported by Agencia Nacional de Investigación e Innovación (ANII) through project FMV_2_2011_1_6971 and PEDECIBA, Uruguay.
Conflict-of-interest: The authors do not have any conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Pilar Moreno, PhD, Laboratorio de Virología Molecular, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Mataojo 2055, 11400 Montevideo, Uruguay.
Telephone: +598-2-5250800 Fax: +598-2-5250895
Received: August 13, 2014
Peer-review started: August 14, 2014
First decision: September 16, 2014
Revised: January 29, 2015
Accepted: February 9, 2015
Article in press: February 11, 2015
Published online: April 28, 2015

Hepatitis C virus (HCV) has infected over 170 million people worldwide and creates a huge disease burden due to chronic, progressive liver disease. HCV is a single-stranded, positive sense, RNA virus, member of the Flaviviridae family. The high error rate of RNA-dependent RNA polymerase and the pressure exerted by the host immune system, has driven the evolution of HCV into 7 different genotypes and more than 67 subtypes. HCV evolves by means of different mechanisms of genetic variation. On the one hand, its high mutation rates generate the production of a large number of different but closely related viral variants during infection, usually referred to as a quasispecies. The great quasispecies variability of HCV has also therapeutic implications since the continuous generation and selection of resistant or fitter variants within the quasispecies spectrum might allow viruses to escape control by antiviral drugs. On the other hand HCV exploits recombination to ensure its survival. This enormous viral diversity together with some host factors has made it difficult to control viral dispersal. Current treatment options involve pegylated interferon-α and ribavirin as dual therapy or in combination with a direct-acting antiviral drug, depending on the country. Despite all the efforts put into antiviral therapy studies, eradication of the virus or the development of a preventive vaccine has been unsuccessful so far. This review focuses on current available data reported to date on the genetic mechanisms driving the molecular evolution of HCV populations and its relation with the antiviral therapies designed to control HCV infection.

Keywords: Recombination, Quasispecies, Hepatitis C virus, RNA, Evolution, Antiviral therapy

Core tip: Hepatitis C virus (HCV) is the major causative agent of parenterally-acquired hepatitis. To date there is no preventive vaccine, and though antiviral therapy has been improved in the past few years, not all patients eradicate the virus as a result of it. The main reason lies in the intrinsic genetic variability that characterises RNA viruses, such as HCV, whose RNA polymerase lacks proof-reading activity, leading to a high mutation rate and the generation of a wide range of genome variants better known as a quasispecies. Therefore this review summarises current data on HCV quasispecies dynamics, antiviral therapy and recombination events.