High Anti-Dengue Virus Activity of the OAS Gene Family Is Associated With Increased Severity of Dengue

J Infect Dis. 2015 Dec 15;212(12):2011-20. doi: 10.1093/infdis/jiv321. Epub 2015 Jun 10.


Dengue is a mosquito-borne viral disease that afflicts millions of individuals worldwide every year. Infection by any of the 4 dengue virus (DENV) serotypes can result in a spectrum of disease severity. We investigated the impact of variants of interferon-regulated innate immunity genes with a potent antiviral effect on the outcome of DENV infection. We compared the effect of OAS gene family variants on 2 DENV serotypes in cell culture. While both OAS1-p42 and p46 showed antiviral activity against DENV-2, only OAS1-p42 presented anti-DENV-1 activity. Conversely, whereas both OAS3_S381 and R381 variants were able to block DENV-1 infection, the anti-DENV-2 activity observed for OAS3_S381 was largely lost for the R381 variant. By means of an allelic association study of a cohort of 740 patients with dengue, we found a protective effect of OAS3_R381 against shock (odds ratio [OR], 0.37; P < .001). This effect was due to DENV-2 infections (OR, 0.13; P = .007) but was absent for DENV-1, in accordance with the serotype-dependent OAS3 activity found in the functional study. Severe dengue has long been associated with a cytokine storm of unclear origin. This work identifies an early innate immunity process that could lead to the immune overreaction observed in severe dengue and could be triggered by a specific host genotype-pathogen genotype interaction.

Keywords: cytokine storm; dengue virus; genetic susceptibility; innate immunity; interferon.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2',5'-Oligoadenylate Synthetase / genetics*
  • 2',5'-Oligoadenylate Synthetase / metabolism
  • Adolescent
  • Adult
  • Cells, Cultured
  • Child
  • Child, Preschool
  • Dengue / genetics
  • Dengue / immunology
  • Dengue / pathology*
  • Dengue Virus / immunology*
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Humans
  • Infant
  • Male
  • Young Adult


  • OAS1 protein, human
  • 2',5'-Oligoadenylate Synthetase
  • OAS3 protein, human