The development of direct-acting antivirals (DAAs) has revolutionized the state-of-the art treatment of HCV infections, with sustained virologic response rates above 90%. However, viral variants harboring substitutions referred to as resistance-associated substitutions (RASs) may be present in baseline levels and confer resistance to DAAs, thereby posing a major challenge for HCV treatment. HCV replicons have been the primary tools for discovering and evaluating the inhibitory activity of DAAs against viral replication. Interest in replicon systems has further grown as they have become indispensable for discovering genotype-specific and cross-genotype RASs. Here, we review functional replicon systems for HCV, how these replicon systems have contributed to the development of DAAs, and the characteristics and distribution of RASs for DAAs.

直接作用抗病毒药（DAA）的发展彻底改变了HCV感染的最新治疗方法，其持续的病毒学应答率超过90％。然而，携带被称为抗性相关替代（RAS）的替代病毒变异体可能会出现在基线水平并赋予对DAA的抗性，从而对HCV治疗提出了重大挑战。HCV复制子已成为发现和评估DAA对病毒复制的抑制活性的主要工具。由于复制子系统对于发现基因型特异性和交叉基因型RAS必不可少，因此人们对其的兴趣进一步增加。在这里，我们回顾了用于HCV的功能复制子系统，这些复制子系统如何促进DAA的发展以及DAA RAS的特征和分布。