The Center for the Study of Hepatitis C, The Rockefeller University, New York, New York 10065, USA.
Annu Rev Microbiol. 2011;65:307-27. doi: 10.1146/annurev-micro-090110-102954.
The reality of hepatitis C is inescapable for the estimated 130 million people worldwide chronically infected with the virus. Yet this pathogen has been notoriously difficult to move from the infected individual into experimental systems, and each advance--from the identification of the infectious agent to its culture and study--has been a significant challenge. As a result of unrelenting technical hurdles, preventative and therapeutic options have been slow to reach hepatitis C patients. More than 35 years since the recognition of the disease, there is no vaccine available, and the only approved treatment, a combination of pegylated interferon-alpha (IFN-α) and ribavirin, is frequently ineffective. Decades of research, however, have resulted in systematic progress and much is now known about this once elusive pathogen. Most importantly, key breakthroughs have stimulated drug discovery, and the first generation of specifically targeted antiviral inhibitors is poised to enter the market. This review provides a look back at progress in developing tractable model systems for this important agent of chronic hepatitis.
全球约有 1.3 亿人慢性感染丙型肝炎病毒,丙型肝炎的现实无法回避。然而,这种病原体一直难以从受感染个体转移到实验系统中,每一次进展——从发现感染因子到培养和研究——都是一个重大挑战。由于技术障碍的持续存在,预防和治疗丙型肝炎的方法迟迟未能惠及丙型肝炎患者。自该疾病被发现以来已经过去了 35 多年,仍然没有可用的疫苗,唯一获得批准的治疗方法是聚乙二醇干扰素-α(IFN-α)和利巴韦林的联合治疗,但通常效果不佳。然而,经过几十年的研究,已经取得了系统性的进展,现在对这种曾经难以捉摸的病原体有了更多的了解。最重要的是,关键的突破刺激了药物发现,第一代专门针对抗病毒抑制剂即将进入市场。这篇综述回顾了开发针对这种重要慢性肝炎病原体的可行模型系统方面的进展。