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Simon-Loriere, Etienne; Lin, Ren-Jye; Kalayanarooj, Sita Mint; Chuansumrit, Ampaiwan; Casademont, Isabelle; Lin, Shyr-Yi; Yu, Han-Pang; Lert-itthiporn, Worachart; Chaiyaratana, Wathanee; Tangthawornchaikul, Nattaya; Tangnararatchakit, Kanchana; Vasanawathana, Sirijitt; Chang, Bi-Lan; Suriyaphol, Prapat; Yoksan, Sutee; Malasit, Prida; Despres, Philipe; Paul, Richard; Lin, Yi-Ling; Sakuntabhai, Anavaj

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

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  • Media type: E-Article
  • Title: High Anti-Dengue Virus Activity of the OAS Gene Family Is Associated With Increased Severity of Dengue
  • Contributor: Simon-Loriere, Etienne; Lin, Ren-Jye; Kalayanarooj, Sita Mint; Chuansumrit, Ampaiwan; Casademont, Isabelle; Lin, Shyr-Yi; Yu, Han-Pang; Lert-itthiporn, Worachart; Chaiyaratana, Wathanee; Tangthawornchaikul, Nattaya; Tangnararatchakit, Kanchana; Vasanawathana, Sirijitt; Chang, Bi-Lan; Suriyaphol, Prapat; Yoksan, Sutee; Malasit, Prida; Despres, Philipe; Paul, Richard; Lin, Yi-Ling; Sakuntabhai, Anavaj
  • Published: Oxford University Press, 2015
  • Published in: The Journal of Infectious Diseases, 212 (2015) 12, Seite 2011-2020
  • Language: English
  • ISSN: 0022-1899
  • Keywords: MAJOR ARTICLES AND BRIEF REPORTS
  • Origination:
  • Footnote:
  • Description: 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.
  • Access State: Open Access