Kato N, Ootsuyama Y, Ohkoshi S, Nakazawa T, Sekiya H, Hijikata M, Shimotohno K
Virology Division, National Cancer Center Research Institute, Tokyo, Japan.
Biochem Biophys Res Commun. 1992 Nov 30;189(1):119-27. doi: 10.1016/0006-291x(92)91533-v.
We previously identified two hypervariable regions [HVR1 (27 amino acids) and HVR2 (7 amino acids)] in the putative envelope glycoprotein (gp70) by comparison of the amino acid sequences of many isolates of the HCV-II genotype. To understand the functional features of these HVRs, using the polymerase chain reaction we analyzed the rate of actual sequence variability in the region including HVR1 and HVR2 of HCV isolated successively at intervals of several months from two patients with chronic C-type hepatitis. In both patients, the amino acid sequence of HVR1, but not HVR2, was found to change dramatically during the observation period (about one amino acid per month). However, no alteration of the amino acid sequence of HVR1 of HCV was observed in a patient in the acute phase of chronic hepatitis. Restriction digestion analysis of sequence diversity showed that a HCV genome with a newly introduced mutation in HVR1 often became the predominant population at the next time of examination. Alterations of amino acids in HVR1 occurred sequentially in the two patients in the chronic phase. These findings suggest that mutations in HVR1 are involved in the mechanism of persistent chronic HCV infection.
我们先前通过比较丙型肝炎病毒II型（HCV-II）许多分离株的氨基酸序列，在假定的包膜糖蛋白（gp70）中鉴定出两个高变区[高变区1（HVR1，27个氨基酸）和高变区2（HVR2，7个氨基酸）]。为了解这些高变区的功能特性，我们利用聚合酶链反应分析了从两名慢性丙型肝炎患者身上每隔数月相继分离出的HCV中包括HVR1和HVR2区域的实际序列变异率。在两名患者中，均发现HVR1的氨基酸序列在观察期内发生了显著变化（每月约一个氨基酸），而HVR2未出现这种情况。然而，在慢性肝炎急性期的一名患者中，未观察到HCV的HVR1氨基酸序列发生改变。序列多样性的限制性酶切分析表明，HVR1中出现新引入突变的HCV基因组在下次检测时往往会成为优势种群。两名慢性期患者的HVR1氨基酸变化是依次发生的。这些发现提示，HVR1中的突变参与了HCV持续慢性感染的机制。
