丙型肝炎病毒非结构 5A 蛋白对干扰素信号的调节：基因型差异对干扰素治疗的影响。

Modulation of interferon signaling by hepatitis C virus non-structural 5A protein: implication of genotypic difference in interferon treatment.

机构信息

National Research Laboratory of Hepatitis C Virus, Ilsong Institute of Life Science, Hallym University, Dongan-gu, Anyang, Republic of Korea.

出版信息

FEBS Lett. 2010 Sep 24;584(18):4069-76. doi: 10.1016/j.febslet.2010.08.032.

DOI:10.1016/j.febslet.2010.08.032

PMID:20804757

Abstract

Interferon (IFN) response rate in hepatitis C virus (HCV) patients has been varied with genotypes. In this study, we investigated the effects of HCV NS5A protein on IFN resistance and compared the genotypic differences of NS5A. We showed that IFN-α-, poly I:C-, and Sendai virus-induced ISRE transcriptional activities were inhibited by both genotype 1b and 2a NS5A protein. We demonstrated that not only genotype 1b but also genotype 2a NS5A exerted the similar extent of IFN-α-induced antiviral activity. We showed that NS5A derived from both genotype 1b and 2a showed no significant differential IFN responses as seen in HCV patients. These data imply that some other host factor may be involved in genotypic differences of IFN antagonism in HCV patients.

摘要

丙型肝炎病毒（HCV）患者的干扰素（IFN）反应率因基因型而异。在这项研究中，我们研究了 HCV NS5A 蛋白对 IFN 耐药性的影响，并比较了 NS5A 的基因型差异。我们表明，1b 型和 2a 型 NS5A 蛋白均可抑制 IFN-α、多聚 I:C 和仙台病毒诱导的 ISRE 转录活性。我们证明，不仅 1b 型，而且 2a 型 NS5A 也发挥了类似程度的 IFN-α诱导的抗病毒活性。我们表明，来自 1b 型和 2a 型的 NS5A 均未显示出 HCV 患者中所见的 IFN 反应的显著差异。这些数据表明，在 HCV 患者中，IFN 拮抗的基因型差异可能涉及某些其他宿主因素。