PDF(Pubmed)
Abstract：
Type I Interferons (IFNs), including numerous IFNα subtypes and IFNβ, are key molecules during innate and adaptive immune responses against viral infections. These cytokines exert various non-redundant biological activities, although binding to the same receptor. Persistent viral infections are often characterized by increased IFN signatures implicating a potential role of type I IFNs in disease pathogenesis. Using the well-established Friend retrovirus (FV) mouse model, we compared the therapeutic efficacy of IFNα11 and IFNβ in acute and chronic retroviral infection. We observed a strong antiviral activity of both IFNs during acute FV infection, whereas only IFNα11 and not IFNβ could also control persistent FV infection. The therapeutic treatment with IFNα11 induced the expression of antiviral IFN-stimulated genes (ISG) and improved cytotoxic T cell responses. Finally, dysfunctional CD8+ T cells solely regained cytotoxicity after IFNα11 treatment. Our data provide evidence for opposing activities of type I IFNs during chronic retroviral infections. IFNβ was shown to be involved in immune dysfunction in chronic infections, whereas IFNα11 had a strong antiviral potential and reactivated exhausted T cells during persistent retroviral infection. In contrast, during acute infection, both type I IFNs were able to efficiently suppress FV replication.
摘要：
I型干扰素（IFN），包括许多IFNα亚型和IFNβ，是针对病毒感染的先天和适应性免疫应答过程中的关键分子。这些细胞因子发挥各种非冗余的生物学活性，虽然与相同的受体结合。持续的病毒感染通常以增加的IFN特征为特征,其暗示I型IFN在疾病发病机理中的潜在作用。使用完善的Friend逆转录病毒（FV）小鼠模型，我们比较了IFNα11和IFNβ在急性和慢性逆转录病毒感染中的疗效。我们观察到在急性FV感染期间两种IFN的强大抗病毒活性，而只有IFNα11而不是IFNβ也可以控制持续性FV感染。用IFNα11的治疗性处理诱导抗病毒IFN刺激基因(ISG)的表达并改善细胞毒性T细胞应答。最后,IFNα11治疗后，功能失调的CD8+T细胞仅恢复了细胞毒性。我们的数据为慢性逆转录病毒感染期间I型IFN的相反活性提供了证据。IFNβ被证明参与慢性感染的免疫功能障碍，而IFNα11有很强的抗病毒潜能,在持续的逆转录病毒感染过程中可以重新激活耗尽的T细胞.相比之下,在急性感染期间，两种I型IFN均能有效抑制FV复制。
