Characterization of hypervariable region in hepatitis C virus envelope protein during acute and chronic infection
Characterization of hypervariable region in hepatitis C virus envelope protein during acute and chronic infection
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DOI：
10.1007/s00705-004-0470-0
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发表时间：
2005-05-01
影响因子：
2.7
通讯作者：
Kohara, M
中科院分区：
文献类型：
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作者：
Higashi, K;Tsukiyama-Kohara, K;Kohara, M
丙型肝炎病毒（HCV）在大多数患者中引起持续感染。为了阐明建立这种持续感染的机制，E1/E2区的核苷酸序列的特点，在5例急性和慢性HCV感染。我们使用直接DNA测序方法来确定每个患者的HCV主要序列。每个HCV基因组在E2的高变区（HVR）中显示出高频率的核苷酸序列变异。然而，在感染过程中，在E1/E2区鉴定出患者特异性保守核苷酸序列，并保守高级蛋白质结构，在急性期HCV感染中，HVR-1中的氨基酸替换，即每个位点之间的氨基酸替换的月速率（%）超过10.2%。在慢性期HCV感染中，观察到患者的氨基酸取代率显著降低。使用合成肽和ELISA表征来自所有临床过程的每个HCV分离株对HVR-1的宿主免疫应答。一名慢性患者血清（基因型1b）对其自身的HVR-1肽完全不反应，然而另一名患者（基因型2b）对所有临床过程都有反应。这些结果表明，HVR-1可能并不总是表现出HCV感染的中和表位。相反，HVR-1中的序列变异可能表明在急性期感染中存在各种克隆，并且这些克隆的适应被认为在每个患者中引起了持续和慢性感染。
Hepatitis C virus (HCV) causes persistent infection in most patients. To clarify the mechanisms underlying establishment of this persistent infection, nucleotide sequences of the E1/E2 region were characterized in 5 patients with acute and chronic HCV infection. We used direct DNA sequencing methods to identify the major sequence of HCV in each patient. Each HCV genome displayed a high frequency of nucleotide sequence variation in the hypervariable region (HVR) of E2. However, patient-specific conserved nucleotide sequences were identified in the E1/E2 region during the course of infection and conserved the higher-order protein structure.In the acute phase HCV infection, amino acid substitution in HVR-1 as the monthly rate of amino acids substitution per site (%) between each point exceeded 10.2%. In the chronic phase HCV infection, a significantly lower rate of amino acid substitution was observed in patients. The host immune responses to HVR-1 of each HCV isolates from all clinical courses were characterized using synthetic peptides and ELISA. One chronic patient serum (genotype 1b) did not react at all to its own HVR-1 peptides, however another patient (genotype 2b) reacted to all clinical course. These results indicated that HVR-1 might not always exhibit neutralizing epitopes of HCV infection. The sequence variation in HVR-1 may instead indicate the existence of various clones in acute phase infection and the adaption of these clones is thought to have caused persistent and chronic infection in each patient.