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

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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Cell Line
  • Cohort Studies
  • DNA, Viral / immunology
  • Gene Frequency
  • Genetic Association Studies
  • Genotype*
  • Herpes Genitalis / immunology*
  • Herpesvirus 2, Human / immunology*
  • Humans
  • Interferon-beta / metabolism*
  • Male
  • Mice
  • Middle Aged
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Phosphoproteins / genetics*
  • Phosphoproteins / metabolism
  • Polymorphism, Single Nucleotide
  • Up-Regulation
  • Young Adult


  • DNA, Viral
  • Nuclear Proteins
  • Phosphoproteins
  • IFI16 protein, human
  • Interferon-beta