Larrea E, Alberdi A, Castelruiz Y, Boya P, Civeira M P, Prieto J
Department of Medicine and Liver Unit, Clínica Universitaria, University of Navarra, 31008 Pamplona, Spain.
J Viral Hepat. 2001 Mar;8(2):103-10. doi: 10.1046/j.1365-2893.2001.00273.x.
Interferon (IFN)-alpha is a family of antiviral proteins encoded by different genes. The biological significance of the existence of various IFN-alpha subtypes is not clear. We have investigated the interferon system in chronic hepatitis C virus (HCV) infection, a disease that responds to interferon-alpha2 therapy in only a limited proportion of cases. We analysed the expression of interferon regulatory factor (IRF)-1, IRF-2, and IFN-alpha subtypes in nonstimulated and Sendai virus-stimulated peripheral blood mononuclear cells (PBMC) from HCV infected patients and healthy controls. We observed that the IRF-1 mRNA and IRF-1/IRF-2 ratios were increased in PBMC from hepatitis C patients with respect to normal subjects. Sendai virus stimulation of PBMC led to a significant increase in the levels of IRF-1, IRF-2 and IFN-alpha mRNAs and in the production of IFN-alpha protein with respect to basal values in healthy controls as well as in patients with HCV infection. In addition, we found that while natural HCV infection induced increased IFN-alpha5 expression in PBMC, in vitro infection of these cells with Sendai virus caused a raise in the expression of IFN-alpha8 in both patients and normal controls. In summary, our results indicate that virus-induced activation of the IFN system in human PBMC is associated with selective expression of individual IFN-alpha subtypes, IFN-alpha5 being the specific subtype induced in PBMC from patients with chronic HCV infection.
干扰素（IFN）-α是由不同基因编码的一类抗病毒蛋白。多种IFN-α亚型存在的生物学意义尚不清楚。我们研究了慢性丙型肝炎病毒（HCV）感染中的干扰素系统，在这种疾病中，只有有限比例的病例对干扰素-α2治疗有反应。我们分析了来自HCV感染患者和健康对照的未刺激及经仙台病毒刺激的外周血单个核细胞（PBMC）中干扰素调节因子（IRF）-1、IRF-2和IFN-α亚型的表达。我们观察到，与正常受试者相比，丙型肝炎患者PBMC中的IRF-1 mRNA和IRF-1/IRF-2比值升高。仙台病毒刺激PBMC导致健康对照以及HCV感染患者的IRF-1、IRF-2和IFN-α mRNA水平相对于基础值显著升高，且IFN-α蛋白产生增加。此外，我们发现，虽然自然HCV感染诱导PBMC中IFN-α5表达增加，但用仙台病毒体外感染这些细胞会导致患者和正常对照中IFN-α8表达升高。总之，我们的结果表明，病毒诱导的人PBMC中干扰素系统激活与单个IFN-α亚型的选择性表达相关，IFN-α5是慢性HCV感染患者PBMC中诱导产生的特定亚型。
