遗传 ›› 2013, Vol. 35 ›› Issue (11): 1244-1252.doi: 10.3724/SP.J.1005.2013.01244

• 综述 • 上一篇    下一篇

IL28B基因在HCV感染中的作用和应用前景

马柯, 张阿梅, 夏雪山   

  1. 昆明理工大学生命科学与技术学院, 昆明 650500
  • 收稿日期:2013-06-09 修回日期:2013-07-26 出版日期:2013-11-20 发布日期:2013-10-25
  • 通讯作者: 张阿梅, 博士, 副教授, 研究方向:疾病遗传学。 夏雪山, 教授, 博士生导师, 研究方向:分子病毒学。E-mail: oliverxia2000@aliyun.com E-mail:zam1980@yeah.net
  • 作者简介:马柯, 硕士研究生, 专业方向:分子病毒学。E-mail: make19880710@163.com
  • 基金资助:

    国家自然科学基金项目(编号:81260248), 国家科技支撑计划项目(编号:2011BAI15B01-21, 2012BAI39B01)和云南省、昆明理工大学人才培养项目(编号:2010CI006、KKSY201226148)资助

The function and application of the IL28B gene in HCV infection and treatment

MA Ke, ZHANG A-Mei, XIA Xue-Shan   

  1. Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China
  • Received:2013-06-09 Revised:2013-07-26 Online:2013-11-20 Published:2013-10-25

摘要:

丙型肝炎病毒(Hepatitis C virus, HCV)是造成慢性肝炎、肝硬化乃至肝癌的主要原因之一, 严重威胁人类健康。宿主因素可影响HCV的感染、治疗效果和自然清除率。近期, 欧美多个研究组对自愈和经过治疗的慢性丙型肝炎患者进行了全基因组关联分析(Genome-wide association study, GWAS), 证明IL28B基因(编码IFN-λ3)的单核苷酸多态位点(Single nucleotide polymorphism, SNP)影响HCV患者的治疗效果和自然清除率。IFN-λ3通过与其异源二聚受体IFN-λR1·IL-10R2结合进行信号传导, 上调干扰素刺激基因的表达, 进而发挥抗病毒、抑制肿瘤细胞生长以及免疫调节等生物学功能, 有望成为一种新型抗HCV药物。虽然IL28B基因SNP影响病毒清除的机制尚未清楚, 但其关联分析结果可作为HCV患者临床治疗的辅助指导, 对HCV患者进行IL28B基因遗传易感和功能研究将有助于该病的预防和治疗。

关键词: 丙型肝炎, IL28B基因, 治疗效果, 自然清除率

Abstract:

Hepatitis C virus (HCV) is the etiological factor for Hepatitis C, which is one of the most important pathogenic factors of chronic liver diseases, cirrhosis and even hepatocellular carcinoma. HCV infection brings great threat to human health. Host genetic background could impact HCV infection, viral clearance, and treatment. Recently, some genome-wide association studies (GWAS) of HCV patients were performed. The results showed that single nucleotide polymorphisms (SNPs) of the IL28B gene, which encodes protein IFN-λ3, are associated with viral clearance and treatment effectiveness of HCV patients who were cured by PEG-IFNα combined with ribavirin (RBV). IFN-λ3 interacts with its acceptor, a heterodimer (IFN-λR1•IL-10R2), and upregulates the IFN-stimulated gene factors (ISGF). IFN-λ3 plays roles in antiviral, antitumor, and immunoloregulation, and thus it might become a potential drug for Hepatitis C treatment. However, the mechanism of the IL28B gene in HCV infection and treatment is unclear, and further studies are needed to reveal the veils and provide theoretical basis for developing a new antiviral drug in clinic.

Key words: hepatitis C, the IL28B gene, response to treatment, viral clearance