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J Immunol. 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.

Author information

1
Department of Rheumatology and Inflammation Research, University of Gothenburg, 40530 Gothenburg, Sweden.
2
Department of Infectious Diseases, Aarhus University Hospital, 8200 Aarhus, Denmark.
3
Department of Dermatovenereology, Sahlgrenska University Hospital, 41345 Gothenburg, Sweden.
4
Rheumatology Unit, Department of Medicine, Karolinska University Hospital, Solna, 17176 Stockholm, Sweden.
5
Department of Infectious Diseases, University of Gothenburg, 41346 Gothenborg, Sweden; and.
6
Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark.
7
Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark srp@biomed.au.dk.

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.

PMID:
28893956
DOI:
10.4049/jimmunol.1700385
[Indexed for MEDLINE]

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