“What I cannot create, I do not understand.” Richard Feynman may have championed reasoning from first principles in his famous blackboard missive, but he could just as well have been referring to the plight of a molecular virologist. What cannot be grown in a controlled laboratory setting, we cannot fully understand. The story of the laboratory domestication of hepatitis C virus (HCV) is now a classic example of virologists applying all manner of inventive skill to create cell-based models of infection in order to clarify prospective drug targets. In this review, we highlight key successes and failures that were instructive in achieving cell-based models for HCV studies and drug development. We also emphasize the lessons learned from the ∼40 year saga that may be applicable to viruses yet unknown and uncultured.

“我无法创造的东西，我就不明白。”理查德·费曼（Richard Feynman）可能在他著名的黑板信中提倡从第一原理进行推理，但他也可能指的是分子病毒学家的困境。无法在受控实验室环境中生长的东西，我们无法完全理解。丙型肝炎病毒（HCV）实验室驯化的故事现已成为病毒学家应用各种创造性技能创建基于细胞的感染模型以阐明潜在药物靶点的典型例子。在这篇综述中，我们重点介绍了在实现 HCV 研究和药物开发细胞模型方面具有指导意义的关键成功和失败。我们还强调从 40 年的传奇中吸取的教训，这些教训可能适用于未知和未培养的病毒。