Foong Y Y, Jans D A, Rolph M S, Gahan M E, Mahalingam S
Division of Immunology and Genetics, The John Curtin School of Medical Research, Australian National University, Canberra ACT 0200, Australia.
Virology. 2009 Oct 25;393(2):228-37. doi: 10.1016/j.virol.2009.07.030. Epub 2009 Sep 3.
Interleukin-15 (IL-15) is a potent growth factor for activated T and natural killer (NK) cells, stimulator of memory T cells and plays an important role in viral immunity. To investigate mechanisms underlying the antiviral activity of IL-15, a recombinant vaccinia virus (rVV) encoding murine IL-15 (VV-IL-15) was constructed. Following infection of mice with VV-IL-15, virus titres in the ovaries were significantly reduced compared to mice infected with control VV. Growth of VV-IL-15 was also reduced in nude athymic mice, indicating the antiviral activity of IL-15 does not require T cells. Additionally, VV-IL-15 augmented the cytolytic activity of natural NK cells in the spleen and enhanced interferon (IFN) mRNA expression and transcription factors associated with IFN induction. Using knockout mice and antibody depletion studies, we showed for the first time that the control of VV-IL-15 replication in mice is dependent on NK cells and IFNs and, in their absence, the protective role of IL-15 is abolished.
白细胞介素-15（IL-15）是活化T细胞和自然杀伤（NK）细胞的一种强效生长因子，是记忆T细胞的刺激因子，在病毒免疫中发挥重要作用。为了研究IL-15抗病毒活性的潜在机制，构建了一种编码小鼠IL-15的重组痘苗病毒（rVV）（VV-IL-15）。用VV-IL-15感染小鼠后，与感染对照VV的小鼠相比，卵巢中的病毒滴度显著降低。在无胸腺裸鼠中，VV-IL-15的生长也受到抑制，这表明IL-15的抗病毒活性不需要T细胞。此外，VV-IL-15增强了脾脏中天然NK细胞的细胞溶解活性，并增强了干扰素（IFN）mRNA表达以及与IFN诱导相关的转录因子。通过使用基因敲除小鼠和抗体清除研究，我们首次表明，小鼠体内VV-IL-15复制的控制依赖于NK细胞和IFN，在没有它们的情况下，IL-15的保护作用就会丧失。
