期刊
JOURNAL OF INFECTIOUS DISEASES
卷 212, 期 12, 页码 2011-2020出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiv321
关键词
innate immunity; dengue virus; cytokine storm; genetic susceptibility; interferon
资金
- European Commission [282 378]
- Agence Nationale de la Recherche (ANR) [2010-INTB-1601-01]
- National Science Council [100-2923-B-001-002-MY3]
- Academia Sinica
- Office of the Higher Education Commission
- Mahidol University under the National Research Universities Initiative
- Medical Scholars Program, Mahidol University
- National Research University
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.
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