Kolykhalov A A, Agapov E V, Blight K J, Mihalik K, Feinstone S M, Rice C M
Department of Molecular Microbiology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110-1093, USA.
Science. 1997 Jul 25;277(5325):570-4. doi: 10.1126/science.277.5325.570.
More than 1% of the world's population is chronically infected with hepatitis C virus (HCV). HCV infection can result in acute hepatitis, chronic hepatitis, and cirrhosis, which is strongly associated with development of hepatocellular carcinoma. Genetic studies of HCV replication have been hampered by lack of a bona fide infectious molecular clone. Full-length functional clones of HCV complementary DNA were constructed. RNA transcripts from the clones were found to be infectious and to cause disease in chimpanzees after direct intrahepatic inoculation. This work defines the structure of a functional HCV genome RNA and proves that HCV alone is sufficient to cause disease.
全球超过1%的人口长期感染丙型肝炎病毒(HCV)。HCV感染可导致急性肝炎、慢性肝炎和肝硬化,而肝硬化与肝细胞癌的发生密切相关。HCV复制的遗传学研究因缺乏真正的感染性分子克隆而受阻。构建了HCV互补DNA的全长功能克隆。发现这些克隆的RNA转录本具有感染性,直接肝内接种后可在黑猩猩中引发疾病。这项工作确定了功能性HCV基因组RNA的结构,并证明仅HCV就足以引发疾病。