Constrained genomic and conformational variability of the hypervariable region 1 of hepatitis C virus in chronically infected patients
Constrained genomic and conformational variability of the hypervariable region 1 of hepatitis C virus in chronically infected patients
复制标题
DOI：
10.1046/j.1365-2893.2002.00349.x
复制
发表时间：
2002-05-01
影响因子：
2.5
通讯作者：
Okita, K
中科院分区：
文献类型：
--
作者：
Hino, K;Korenaga, M;Okita, K
我们分析了丙型肝炎病毒 (HCV) 高变区 1 (HVR1) 的基因组和构象变异性，以评估其生物学作用的重要性。从 11 名慢性丙型肝炎患者的连续采样血清中收集了总共 865 个基因型 1b HVR1 亚克隆，其中 4 名患者接受了干扰素治疗。因此，检查了 169 个不同序列的氨基酸取代以及 HVR1 内每个氨基酸位置的亲水性或疏水性特征。 HVR1 的二级结构也通过 Robson 的方法在来自 8 名患者（包括 3 名接受干扰素治疗的患者）的 90 个不同序列中进行了预测。 HVR1内的一些位置是不变的或几乎是氨基酸取代的。亲水性或疏水性残基在几个位置上占主导地位。尽管在干扰素治疗的患者中，HVR1内几乎所有氨基酸位置的氨基酸替换频率都较高，但无论干扰素治疗如何，这些受限氨基酸替换和亲水性或疏水性特征都是保守的。 HCV准种表现出多种HVR1二级结构，但许多序列似乎具有共同特征。可以识别 N 末端和位置 20（从 E2 包膜糖蛋白的 NH2 末端编号）周围的 β 片层构象和/或 HVR1 C 末端周围的卷曲结构。这些结果表明，尽管 HVR1 氨基酸替换能够耐受氨基酸替换，但其氨基酸替换受到良好有序结构的强烈限制，并且暗示 HVR1 蛋白在 HCV 复制中的重要生物学作用。
We analysed the genomic and conformational variability of the hypervariable region 1 (HVR1) of the hepatitis C virus (HCV) to evaluate the importance of its biological role. A total of 865 genotype 1b HVR1 subclones were collected from serially sampled sera in 11 patients with chronic hepatitis C, four of whom received interferon therapy. Consequently, 169 distinct sequences were examined for amino acid substitutions as well as hydrophilic or hydrophobic profile at each amino acid position within HVR1. Secondary structure of HVR1 was also predicted by the method of Robson in 90 distinct sequences from eight patients, including three interferon-treated patients. Some positions within the HVR1 were invariable or nearly so as to amino acid substitution. Hydrophilic or hydrophobic residues exclusively predominated at several positions. These constrained amino acid replacement and hydrophilic or hydrophobic profiles were conserved irrespective of interferon therapy, though the frequency of amino acid replacement was greater at almost all amino acid positions within the HVR1 in interferon-treated patients. The quasispecies of HCV showed various secondary structures of HVR1, but many sequences seemed to have common characteristics. beta sheet conformations around both the N-terminus and position 20 (numbered from the NH2 terminus of E2 envelope glycoprotein), and/or coil structures around the C-terminus of HVR1 could be identified. These results suggest that HVR1 amino acid replacements are strongly constrained by a well-ordered structure, in spite of being tolerant to amino acid substitutions, and imply an important biological role of the HVR1 protein in HCV replication.