High anti- XXXX viral activity of OAS gene family is associated with increased severity of dengue disease.

@entity1 @entity22167 @entity15771 @entity281 @entity1800 @entity9508 @entity779
UNASSIGNED: Dengue is a mosquito-borne @entity1800 that afflicts millions of individuals worldwide every year. Infection by any of the four serotypes can result in a spectrum of disease severity. We investigated the impact of variants of interferon regulated innate immunity genes with a potent anti-viral effect, on the outcome of @entity281 . We compared the effect of OAS gene family variants on two @entity779 virus (DENV) serotypes in cell culture. While both @entity22167 - @entity15771 and p46 showed antiviral activity against DENV-2, only @entity22167 - @entity15771 presented anti-DENV-1 activity. Conversely, whereas both @entity9508 _S381 and R381 variants were able to block DENV-1 infection, the anti-DENV-2 activity observed for @entity9508 _S381 was largely lost for the R381 variant. By allelic association study on a cohort of 740 @entity779 @entity1 , we found a protective effect of @entity9508 _R381 against shock (OR=0.37; P<0.001). This effect was due to DENV-2 infections (OR=0.13, P=0.007), but was absent for DENV-1, in accordance with the serotype-dependent @entity9508 activity found in the functional study. Severe @entity779 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 @entity779 , and triggered by a specific host genotype-pathogen genotype interaction.
