丙型肝炎病毒1b型E2羧基末端区域的突变，包括PKR/eIF2α磷酸化同源结构域和非结构蛋白5A的干扰素敏感性决定区：它们与干扰素单药治疗反应及病毒载量的相关性。

Mutations in carboxy-terminal part of E2 including PKR/eIF2alpha phosphorylation homology domain and interferon sensitivity determining region of nonstructural 5A of hepatitis C virus 1b: their correlation with response to interferon monotherapy and viral load.

作者信息

Ukai Koji, Ishigami Masatoshi, Yoshioka Kentaro, Kawabe Naoto, Katano Yoshiaki, Hayashi Kazuhiko, Honda Takashi, Yano Motoyoshi, Goto Hidemi

机构信息

Division of Liver and Biliary Diseases, Department of Internal Medicine, Fujita Health University School of Medicine, Kutsukake, Toyoake, Aichi, Japan.

出版信息

World J Gastroenterol. 2006 Jun 21;12(23):3722-8. doi: 10.3748/wjg.v12.i23.3722.

DOI:10.3748/wjg.v12.i23.3722

PMID:16773689

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4087465/

Abstract

AIM

To study the amino acid substitutions in the carboxy (C)-terminal part of E2 protein and in the interferon (IFN) sensitivity determining region (ISDR) and their correlation with response to IFN and viral load in 85 hepatitis C virus (HCV)-1b-infected patients treated with IFN.

METHODS

The C-terminal part of E2 (codons 617-711) including PKR/eIF2alpha phosphorylation homology domain (PePHD) and ISDR was sequenced in 85 HCV-1b-infected patients treated by IFN monotherapy.

RESULTS

The amino acid substitutions in PePHD detected only in 4 of 85 patients were not correlated either with response to IFN or with viral load. The presence of substitutions in a N-terminal variable region (codons 617-641) in the C-terminal part of E2 was significantly correlated with both small viral load (33.9% vs 13.8%, P = 0.0394) and sustained response to IFN (25.0% vs 6.9%, P = 0.0429). Four or more substitutions in ISDR were significantly correlated with both small viral load (78.6% vs 16.2%, P < 0.0001) and sustained response to IFN (85.7% vs 2.9%, P < 0.0001). In multivariate analysis, ISDR in nonstructural (NS) 5A (OR = 0.39, P < 0.0001) and N-terminal variable region (OR = 0.51, P = 0.039) was selected as the independent predictors for small viral load, and ISDR (OR = 39.0, P < 0.0001) was selected as the only independent predictor for sustained response.

CONCLUSION

The N-terminal variable region in the C-terminal part of E2 correlates with both response to IFN monotherapy and viral load and is one of the factors independently associated with a small viral load.

摘要

目的

研究85例接受干扰素治疗的丙型肝炎病毒（HCV）-1b感染患者中，E2蛋白羧基（C）末端部分及干扰素（IFN）敏感性决定区（ISDR）的氨基酸替代情况，及其与IFN应答和病毒载量的相关性。

方法

对85例接受干扰素单药治疗的HCV-1b感染患者，对包括PKR/eIF2α磷酸化同源结构域（PePHD）和ISDR的E2蛋白C末端部分（第617至711位密码子）进行测序。

结果

仅在85例患者中的4例检测到的PePHD中的氨基酸替代，与IFN应答或病毒载量均无相关性。E2蛋白C末端的N端可变区（第617至641位密码子）存在替代，与低病毒载量（33.9%对13.8%，P = 0.0394）和对IFN的持续应答（25.0%对6.9%，P = 0.0429）均显著相关。ISDR中四个或更多替代与低病毒载量（78.6%对16.2%，P < 0.0001）和对IFN的持续应答（85.7%对2.9%，P < 0.0001）均显著相关。在多变量分析中，非结构（NS）5A中的ISDR（比值比[OR] = 0.39，P < 0.0001）和N端可变区（OR = 0.51，P = 0.039）被选为低病毒载量的独立预测因子，而ISDR（OR = 39.0，P < 0.0001）被选为持续应答的唯一独立预测因子。