Lindenbach Brett D, Meuleman Philip, Ploss Alexander, Vanwolleghem Thomas, Syder Andrew J, McKeating Jane A, Lanford Robert E, Feinstone Stephen M, Major Marian E, Leroux-Roels Geert, Rice Charles M
Center for the Study of Hepatitis C, Laboratory of Virology and Infectious Disease, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
Proc Natl Acad Sci U S A. 2006 Mar 7;103(10):3805-9. doi: 10.1073/pnas.0511218103. Epub 2006 Feb 16.
Hepatitis C virus (HCV) is a major cause of chronic liver disease, frequently progressing to cirrhosis and increased risk of hepatocellular carcinoma. Current therapies are inadequate and progress in the field has been hampered by the lack of efficient HCV culture systems. By using a recently described HCV genotype 2a infectious clone that replicates and produces infectious virus in cell culture (HCVcc), we report here that HCVcc strain FL-J6/JFH can establish long-term infections in chimpanzees and in mice containing human liver grafts. Importantly, virus recovered from these animals was highly infectious in cell culture, demonstrating efficient ex vivo culture of HCV. The improved infectivity of animal-derived HCV correlated with virions of a lower average buoyant density than HCVcc, suggesting that physical association with low-density factors influences viral infectivity. These results greatly extend the utility of the HCVcc genetic system to allow the complete in vitro and in vivo dissection of the HCV life cycle.
丙型肝炎病毒（HCV）是慢性肝病的主要病因，常进展为肝硬化并增加肝细胞癌风险。目前的治疗方法并不充分，该领域的进展因缺乏有效的HCV培养系统而受阻。通过使用最近描述的在细胞培养中复制并产生感染性病毒的HCV 2a基因型感染性克隆（HCVcc），我们在此报告HCVcc株FL-J6/JFH可在黑猩猩和含有人肝移植物的小鼠中建立长期感染。重要的是，从这些动物中回收的病毒在细胞培养中具有高度传染性，证明了HCV的高效体外培养。动物源性HCV感染性的提高与平均浮力密度低于HCVcc的病毒粒子相关，这表明与低密度因子的物理关联会影响病毒感染性。这些结果极大地扩展了HCVcc遗传系统的用途，从而能够在体外和体内完整剖析HCV的生命周期。
