Brambilla S, Bellati G, Asti M, Lisa A, Candusso M E, D'Amico M, Grassi G, Giacca M, Franchini A, Bruno S, Ideo G, Mondelli M U, Silini E M
Department of Pathology, Università and IRCCS Policlinico San Matteo, Pavia, Italy.
Hepatology. 1998 Jun;27(6):1678-86. doi: 10.1002/hep.510270629.
Hepatitis C virus (HCV) infection is a dynamic process during which molecular variants are continuously selected as the result of virus adaptation to the host. Understanding the nature of HCV genetic variation is central to current theories of pathogenesis and immune response. We prospectively studied hypervariable region 1 (HVR1) variation in the E2 gene of 36 hepatitis C patients, including 10 asymptomatic carriers, followed up for 1 to 2 years. Sequence changes in single and consecutive serum samples were assessed and correlated with clinical and virological parameters of liver disease. A region of the E1 gene was sequenced for comparison in 3 subjects. HVR1 heterogeneity at single time points widely varied in individual patients, did not increase cumulatively over the follow-up period, and did not correlate with HVR1 evolutionary rates. Conversely, the process of HVR1 sequence diversification, although differed considerably among patients, was stable over time and directly correlated with infections by HCV type 2, lower alanine aminotransferase (ALT) levels, and absence of cirrhosis. HCV carriers showed the highest HVR1 variation rates. Our findings indicate that HVR1 variation has an adaptive significance and is associated with favorable features of liver disease and suggest that prospective, rather than static, observations are required to model the process of HCV variation.
丙型肝炎病毒（HCV）感染是一个动态过程，在此过程中，由于病毒对宿主的适应性，分子变异体不断被选择。了解HCV基因变异的本质是当前发病机制和免疫反应理论的核心。我们前瞻性地研究了36例丙型肝炎患者E2基因高变区1（HVR1）的变异情况，其中包括10例无症状携带者，随访时间为1至2年。评估单次和连续血清样本中的序列变化，并将其与肝病的临床和病毒学参数相关联。对3名受试者的E1基因区域进行测序以作比较。在个体患者中，单个时间点的HVR1异质性差异很大，在随访期间没有累积增加，并且与HVR1进化速率无关。相反，HVR1序列多样化过程虽然在患者之间差异很大，但随时间稳定，并且与2型HCV感染、较低的丙氨酸转氨酶（ALT）水平和无肝硬化直接相关。HCV携带者显示出最高的HVR1变异率。我们的研究结果表明，HVR1变异具有适应性意义，并且与肝病的有利特征相关，并表明需要进行前瞻性而非静态观察来模拟HCV变异过程。
