MOLECULAR BIOLOGY OF HEPATITIS C VIRUS

丙型肝炎病毒（HCV）是一种重要的人类病原体， 与输血相关的非甲非乙型肝炎（NANB）有关。 患者H是一名过去一直是慢性HCV携带者的患者 13年 我们比较了核苷酸和预测的氨基酸序列 从1977年收集的血浆中获得的HCV基因组， 在1990年收集，发现两种HCV分离株在123 测序4,923个核苷酸（2.50%）。 我们估计这种突变 HCV的H株的速率约为1.9 × 10-（3）碱基 每个基因组位点的基因替换。 核苷酸的变化是 完全是碱基替换，并且不均匀地分布在整个 基因组具有相对较高的变化率， 非结构蛋白1样基因区。 我们的研究结果表明 HCV基因组的突变率与其他RNA相似， HCV基因似乎以不同的速度进化， 在病毒基因组中。 虽然发展血清学方法检测HCV抗体 极大地扩展了我们对NANB肝炎的认识， 关于HCV感染期间病毒血症的过程。 所以我们 用聚合酶链反应研究了血清HCV RNA的模式 反应测定及其与抗体应答和临床的关系 在NANB肝炎的过程中。 血清HCV RNA首次出现 大多数患者在感染后1周内接受检查 在肝炎临床发作和抗体血清转换之前。 病毒血症是短暂的，在急性自限性 肝炎，但持续长达14年的患者慢性 感染了 血清HCV RNA可提供以下预后信息： 急性病毒感染进展为慢性病毒感染。

Hepatitis C virus (HCV) is an important human pathogen that is strongly associated with transfusion related non-A, non-B (NANB) hepatitis. Patient H is a patient who has been a chronic HCV carrier for the past 13 years. We compared the nucleotide and predicted amino acid sequences of the HCV genome obtained from plasma collected in 1977 with that collected in 1990 and found that the two HCV isolates differ at 123 of the 4,923 (2.50%) nucleotides sequenced. We estimate that the mutation rate of the H strain of HCV is approximately 1.9 x 10-(3) base substitutions per genome site per year. The nucleotide changes were exclusively base substitutions and were unevenly distributed throughout the genome with a relatively high rate of change observed in the nonstructural protein number 1-like gene region. Our results suggest that the mutation rate of the HCV genome is similar to that of other RNA viruses and that HCV genes appear to be evolving at different rates within the virus genome. Although the development of a serologic assay to detect antibody to HCV has greatly extended our knowledge of NANB hepatitis, little is known about the course of viremia during HCV infection. Therefore, we investigated the pattern of serum HCV RNA using the polymerase chain reaction assay and its relationship to antibody response and clinical outcome in the course of NANB hepatitis. Serum HCV RNA first appeared within 1 week post- infection in the majority of patients examined preceding the clinical onset of hepatitis and antibody seroconversion. Viremia was transient, lasting only a few months in acute self-limited hepatitis, but persisted up to 14 years in patients chronically infected. Serum HCV RNA may provide prognostic information regarding progression of acute to chronic virus infection.