Eriksson Kristina, Svensson Alexandra, Hait Alon S, Schlüter Kerstin, Tunbäck Petra, Nordström Inger, Padyukov Leonid, Liljeqvist Jan-Åke, Mogensen Trine H, Paludan Søren R
Department of Rheumatology and Inflammation Research, University of Gothenburg, 40530 Gothenburg, Sweden.
Department of Infectious Diseases, Aarhus University Hospital, 8200 Aarhus, Denmark.
J Immunol. 2017 Oct 15;199(8):2613-2617. doi: 10.4049/jimmunol.1700385. Epub 2017 Sep 11.
IFN-γ-inducible protein 16 (IFI16) is an immunological DNA sensor proposed to act in the cyclic GMP-AMP synthase-stimulator of IFN genes pathway. Because mice do not have a clear ortholog of IFI16, this system is not suitable for genetic studies of IFI16. In this study, we have compared the dependency on IFI16, cyclic GMP-AMP synthase, and stimulator of IFN genes for type I IFN induction by a panel of pathogenic bacteria and DNA viruses. The IFN response induced by HSV-2 was particularly dependent on IFI16. In a cohort of patients with genital herpes and healthy controls, the minor G allele of the single nucleotide polymorphism rs2276404 was associated with resistance to infection. Furthermore, the combination of this allele with the C allele of rs1417806 was significantly overrepresented in uninfected individuals. Cells from individuals with the protective GC haplotype expressed higher levels of IFI16 and induced more IFN-β upon HSV-2 infection. These data provide genetic evidence for a role for IFI16 in protection against genital herpes.
干扰素γ诱导蛋白16（IFI16）是一种免疫性DNA传感器，被认为在环磷酸鸟苷-腺苷合成酶-干扰素基因刺激物途径中发挥作用。由于小鼠没有明确的IFI16直系同源物，该系统不适用于IFI16的遗传学研究。在本研究中，我们比较了一组致病细菌和DNA病毒诱导I型干扰素时对IFI16、环磷酸鸟苷-腺苷合成酶和干扰素基因刺激物的依赖性。单纯疱疹病毒2（HSV-2）诱导的干扰素反应特别依赖于IFI16。在一组生殖器疱疹患者和健康对照中，单核苷酸多态性rs2276404的次要G等位基因与抗感染能力相关。此外，该等位基因与rs1417806的C等位基因的组合在未感染个体中显著富集。具有保护性GC单倍型的个体的细胞表达更高水平的IFI16，并且在HSV-2感染后诱导更多的干扰素-β。这些数据为IFI16在预防生殖器疱疹中的作用提供了遗传学证据。
