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© Research
Publication : The Journal of infectious diseases

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

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in The Journal of infectious diseases - 10 Jun 2015

Simon-Loriere E, Lin RJ, Kalayanarooj SM, Chuansumrit A, Casademont I, Lin SY, Yu HP, Lert-Itthiporn W, Chaiyaratana W, Tangthawornchaikul N, Tangnararatchakit K, Vasanawathana S, Chang BL, Suriyaphol P, Yoksan S, Malasit P, Despres P, Paul R, Lin YL, Sakuntabhai A

Link to Pubmed [PMID] – 26063222

J. Infect. Dis. 2015 Jun;

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.

http://www.ncbi.nlm.nih.gov/pubmed/26063222