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 ErikssonAlexandra SvenssonAlon S HaitKerstin SchlüterPetra TunbäckInger NordströmLeonid PadyukovJan-Åke LiljeqvistTrine H MogensenSoren Riis PaludanPublished in: Journal of immunology (Baltimore, Md. : 1950) (2017)
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.
Keyphrases
- dendritic cells
- immune response
- genome wide
- herpes simplex virus
- poor prognosis
- circulating tumor
- type diabetes
- single molecule
- copy number
- high glucose
- dna methylation
- cell free
- oxidative stress
- metabolic syndrome
- cystic fibrosis
- machine learning
- electronic health record
- pseudomonas aeruginosa
- endothelial cells
- transcription factor
- insulin resistance
- solid phase extraction