Hepatitis C virus genetic variability and evolution  

作　　者：Natalia Echeverría Gonzalo Moratorio Juan Cristina Pilar Moreno 

机构地区：[1]Laboratorio de Virología Molecular, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República [2]Viral Populations and Pathogenesis Laboratory,Institut Pasteur, 75724 Paris CEDEX 15, France [3]Recombinant Proteins Unit, Institut Pasteur de Montevideo,11400 Montevideo, Uruguay

出　　处：《World Journal of Hepatology》2015年第6期831-845,共15页世界肝病学杂志（英文版）（电子版）

基　　金：Agencia Nacional de Investigación e Innovación(ANII)through project FMV_2_2011_1_6971 and PEDECIBA,Uruguay

摘　　要：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 singlestranded, 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.Hepatitis C virus （HCV） has infected over 170 millionpeople worldwide and creates a huge disease burdendue to chronic, progressive liver disease. HCV is a singlestranded,positive sense, RNA virus, member of theFlaviviridae family. The high error rate of RNA-dependentRNA polymerase and the pressure exerted by the hostimmune system, has driven the evolution of HCV into7 different genotypes and more than 67 subtypes. HCVevolves by means of different mechanisms of geneticvariation. On the one hand, its high mutation ratesgenerate the production of a large number of differentbut closely related viral variants during infection, usuallyreferred to as a quasispecies. The great quasispeciesvariability of HCV has also therapeutic implications sincethe continuous generation and selection of resistant orfitter variants within the quasispecies spectrum mightallow viruses to escape control by antiviral drugs. Onthe other hand HCV exploits recombination to ensure itssurvival. This enormous viral diversity together with somehost factors has made it difficult to control viral dispersal.Current treatment options involve pegylated interferon-αand ribavirin as dual therapy or in combination with adirect-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 preventivevaccine has been unsuccessful so far. This review focuseson current available data reported to date on the geneticmechanisms driving the molecular evolution of HCVpopulations and its relation with the antiviral therapiesdesigned to control HCV infection.

关 键 词：Recombination QUASISPECIES Hepatitis Cvirus RNA EVOLUTION Antiviral therapy 

分 类 号：R373[医药卫生—病原生物学]