Echeverría Natalia, Moratorio Gonzalo, Cristina Juan, Moreno Pilar
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.
World J Hepatol. 2015 Apr 28;7(6):831-45. doi: 10.4254/wjh.v7.i6.831.
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.
丙型肝炎病毒（HCV）在全球已感染超过1.7亿人，并因其导致的慢性进行性肝病而造成巨大的疾病负担。HCV是一种单链、正义RNA病毒，属于黄病毒科。RNA依赖性RNA聚合酶的高错误率以及宿主免疫系统施加的压力，促使HCV进化为7种不同的基因型和67种以上的亚型。HCV通过不同的遗传变异机制进化。一方面，其高突变率在感染期间产生大量不同但密切相关的病毒变体，通常称为准种。HCV的巨大准种变异性也具有治疗意义，因为在准种谱内持续产生和选择抗性或更适应的变体可能使病毒逃避抗病毒药物的控制。另一方面，HCV利用重组来确保其生存。这种巨大的病毒多样性以及一些宿主因素使得控制病毒传播变得困难。目前的治疗选择包括聚乙二醇化干扰素-α和利巴韦林作为联合疗法，或者根据国家情况与直接作用抗病毒药物联合使用。尽管在抗病毒治疗研究方面付出了所有努力，但迄今为止，根除病毒或开发预防性疫苗均未成功。本综述重点关注迄今报道的有关驱动HCV群体分子进化的遗传机制及其与旨在控制HCV感染的抗病毒疗法之间关系的现有数据。
