Clementi M
San Raffaele Vita-Salute University, San Raffaele Laboratory of Microbiology, Diagnostics and Research, San Raffaele Scientific Institute IRCCS, Milan, Italy.
J Biol Regul Homeost Agents. 2003 Apr-Jun;17(2):120-4.
The HCV genome exhibits significant intra-host genetic heterogeneity as the result of accumulation of mutations during viral replication. At each point in time during the infection, the viral population is composed of a dominant master sequence and a number of sequences diverging from the master sequence to various extents (the viral quasi-species). The quasispecies is a complex, dynamic distribution of nonidentical, but related, replicons. In these populations, viral variants may undergo very large changes in their fitness (the replicative adaptability of an organism to its environment), including dramatic fitness loss and important fitness gains. The biological impact of this event may theoretically include modifications of tropism, appearance of escape mutants, changes in pathogenic potential, and resistance to antiviral agents. A growing body of molecular and clinical data currently suggests that both inter- and intra-host genetic heterogeneity of HCV have crucial biological and medical implications, influencing not only infection prevention, but also clinical progression of chronic liver disease in persistently infected subjects, HCV infection of non-liver cells, and response to the anti-viral therapy.
由于病毒复制过程中突变的积累，丙型肝炎病毒（HCV）基因组表现出显著的宿主内遗传异质性。在感染期间的每个时间点，病毒群体由一个占主导地位的主序列和一些与主序列在不同程度上有差异的序列组成（病毒准种）。准种是一组复杂的、动态分布的非同一但相关的复制子。在这些群体中，病毒变体的适应性（生物体对其环境的复制适应性）可能会发生非常大的变化，包括显著的适应性丧失和重要的适应性增加。从理论上讲，这一事件的生物学影响可能包括嗜性改变、逃逸突变体的出现、致病潜力的变化以及对抗病毒药物的耐药性。目前越来越多的分子和临床数据表明，HCV的宿主间和宿主内遗传异质性都具有关键的生物学和医学意义，不仅影响感染的预防，还影响持续感染患者慢性肝病的临床进展、非肝细胞的HCV感染以及抗病毒治疗的反应。
