Institute for Virology of the University Hospital in Essen, University of Duisburg-Essen, Essen, Germany.
PLoS Pathog. 2012;8(8):e1002868. doi: 10.1371/journal.ppat.1002868. Epub 2012 Aug 9.
The innate immune response mediated by cells such as natural killer (NK) cells is critical for the rapid containment of virus replication and spread during acute infection. Here, we show that subtype 11 of the type I interferon (IFN) family greatly potentiates the antiviral activity of NK cells during retroviral infection. Treatment of mice with IFN-α11 during Friend retrovirus infection (FV) significantly reduced viral loads and resulted in long-term protection from virus-induced leukemia. The effect of IFN-α11 on NK cells was direct and signaled through the type I IFN receptor. Furthermore, IFN-α11-mediated activation of NK cells enabled cytolytic killing of FV-infected target cells via the exocytosis pathway. Depletion and adoptive transfer experiments illustrated that NK cells played a major role in successful IFN-α11 therapy. Additional experiments with Mouse Cytomegalovirus infections demonstrated that the therapeutic effect of IFN-α11 is not restricted to retroviruses. The type I IFN subtypes 2 and 5, which bind the same receptor as IFN-α11, did not elicit similar antiviral effects. These results demonstrate a unique and subtype-specific activation of NK cells by IFN-α11.
细胞（如自然杀伤 (NK) 细胞）介导的固有免疫反应对于急性感染期间迅速遏制病毒复制和传播至关重要。在这里，我们表明 I 型干扰素 (IFN) 家族的 11 型亚类在逆转录病毒感染期间极大地增强了 NK 细胞的抗病毒活性。在 Friend 逆转录病毒感染 (FV) 期间用 IFN-α11 治疗小鼠可显著降低病毒载量，并从病毒诱导的白血病中获得长期保护。IFN-α11 对 NK 细胞的作用是直接的，并通过 I 型 IFN 受体发出信号。此外，IFN-α11 介导的 NK 细胞激活通过胞吐途径使 FV 感染的靶细胞发生细胞溶解杀伤。耗尽和过继转移实验表明 NK 细胞在 IFN-α11 治疗中起主要作用。用小鼠巨细胞病毒感染进行的其他实验表明，IFN-α11 的治疗效果不限于逆转录病毒。与 IFN-α11 结合相同受体的 I 型 IFN 亚型 2 和 5 并未引起类似的抗病毒作用。这些结果表明 IFN-α11 对 NK 细胞具有独特的、亚型特异性的激活作用。
