High anti-dengue virus activity of the OAS gene family is associated with increased severity of dengue

Abstract

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