Mutations within the Hepatitis C Virus Genotype 1b E2-PePHD Domain Do Not Correlate with Treatment Outcome
Mutations within the Hepatitis C Virus Genotype 1b E2-PePHD Domain Do Not Correlate with Treatment Outcome
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丙型肝炎病毒基因型 1b E2-PePHD 结构域内的突变与治疗结果不相关
DOI：
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发表时间：
2005
影响因子：
9.4
通讯作者：
A. Goudeau
中科院分区：
文献类型：
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作者：
C. Gaudy;Marie Lambelé;A. Moreau;P. Veillon;F. Lunel;A. Goudeau
摘要丙型肝炎病毒包膜蛋白2(E_2)在体外与干扰素-α诱导的双链核糖核酸活化蛋白激酶相互作用，提示丙型肝炎病毒逃避干扰素-α抗病毒作用的可能机制。对25例丙型肝炎病毒1b型感染者和接受干扰素-α治疗的患者进行了丙型肝炎病毒E2基因编码区变异的研究。对15例持续应答的患者和10例经干扰素-α和利巴韦林治疗后无病毒学应答的患者进行聚合酶链式反应产物的产生和测序。从治疗前和治疗期间、应答者2个月后和无应答者6个月后收集的血清中获得PePHD氨基酸序列。对直接测序显示该区域存在氨基酸替换的患者的分离物进行了前PePHD区域的准种分析。E2-PePHD序列在1b型耐药株和易感株中都高度保守，与典型的丙型肝炎病毒J型序列完全相同。在我们的克隆分析中没有观察到治疗期间出现显著的PePHD突变，也没有发现零星突变与治疗结果相关。治疗前或治疗期间的PePHD序列不能可靠地预测丙型肝炎病毒1b型感染患者的治疗结果。
ABSTRACT The hepatitis C virus (HCV) envelope protein 2 (E2) interacts in vitro with the interferon alpha (IFN-α)-inducible double-stranded RNA-activated protein kinase, suggesting a possible mechanism by which HCV may evade the antiviral effects of IFN-α. Variability in the part of the HCV E2 gene encoding the carboxy-terminal part of the protein, which includes the interaction domain (E2-PePHD), was explored in 25 patients infected with HCV genotype 1b and receiving IFN-α therapy. PCR products were generated and sequenced for 15 patients with a sustained response and for 10 patients with no virological response after treatment with IFN-α and ribavirin. PePHD amino acid sequences were obtained for isolates from serum collected before and during treatment, after 2 months in responders, and after 6 months in nonresponders. Quasispecies analysis of the pretreatment PePHD region was performed for isolates from patients displaying amino acid substitutions in this domain on direct sequencing. The E2-PePHD sequence was highly conserved in both resistant and susceptible genotype 1b strains and was identical to the prototype HCV type J sequence. No significant emergence of PePHD mutants during therapy was observed in our clonal analysis, and sporadic mutations and treatment outcomes were not found to be correlated. The PePHD sequence before or during treatment cannot be used to predict reliably the outcome of treatment in HCV type 1b-infected patients.
影响因子：
56.9
作者：
Taylor, DR;Shi, ST;Lai, MMC
通讯作者：
Lai, MMC