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. 2017 Oct 15;199(8):2613-2617.
doi: 10.4049/jimmunol.1700385. Epub 2017 Sep 11.

Cutting Edge: Genetic Association Between IFI16 Single Nucleotide Polymorphisms and Resistance to Genital Herpes Correlates With IFI16 Expression Levels and HSV-2-Induced IFN-β Expression

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Cutting Edge: Genetic Association Between IFI16 Single Nucleotide Polymorphisms and Resistance to Genital Herpes Correlates With IFI16 Expression Levels and HSV-2-Induced IFN-β Expression

Kristina Eriksson et al. J Immunol. .
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Abstract

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 IFI16 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.

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