title: 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 < .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.
authors.affiliation: Unité de Génétique Fonctionnelle des Maladies Infectieuses, Department Genome and Genetics Centre National de la Recherche Scientifique, URA3012, Paris, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Simon-Loriere
authors.affiliation: Department of General Medicine, School of Medicine, College of Medicine, Taipei Medical University Department of Primary Care Medicine, Taipei Medical University Hospital, Taipei City.
authors.forename: Ren-Jye
authors.initials: RJ
authors.lastname: Lin
authors.affiliation: Dengue Hemorrhagic Fever Research Unit Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University.
authors.forename: Sita Mint
authors.initials: SM
authors.lastname: Kalayanarooj
authors.affiliation: Department of Pediatrics.
authors.forename: Ampaiwan
authors.initials: A
authors.lastname: Chuansumrit
authors.affiliation: Unité de Génétique Fonctionnelle des Maladies Infectieuses, Department Genome and Genetics Centre National de la Recherche Scientifique, URA3012, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Casademont
authors.affiliation: Department of General Medicine, School of Medicine, College of Medicine, Taipei Medical University Department of Primary Care Medicine, Taipei Medical University Hospital, Taipei City.
authors.forename: Shyr-Yi
authors.initials: SY
authors.lastname: Lin
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Nankang, Taiwan.
authors.forename: Han-Pang
authors.initials: HP
authors.lastname: Yu
authors.affiliation: Division of Bioinformatics and Data Management for Research, Department of Research and Development, Faculty of Medicine, Siriraj Hospital Molecular Medicine Graduate Program.
authors.forename: Worachart
authors.initials: W
authors.lastname: Lert-Itthiporn
authors.affiliation: Research Center, Faculty of Medicine, Ramathibodi Hospital.
authors.forename: Wathanee
authors.initials: W
authors.lastname: Chaiyaratana
authors.affiliation: Medical Biotechnology Research Unit, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Bangkok.
authors.forename: Nattaya
authors.initials: N
authors.lastname: Tangthawornchaikul
authors.affiliation: Department of Pediatrics.
authors.forename: Kanchana
authors.initials: K
authors.lastname: Tangnararatchakit
authors.affiliation: Pediatric Department, Khon Kaen Hospital, Ministry of Public Health.
authors.forename: Sirijitt
authors.initials: S
authors.lastname: Vasanawathana
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Nankang, Taiwan.
authors.forename: Bi-Lan
authors.initials: BL
authors.lastname: Chang
authors.affiliation: Division of Bioinformatics and Data Management for Research, Department of Research and Development, Faculty of Medicine, Siriraj Hospital Center for Emerging and Neglected Infectious Diseases.
authors.forename: Prapat
authors.initials: P
authors.lastname: Suriyaphol
authors.affiliation: Center for Vaccine Development, Institute of Science and Technology for Research and Development, Mahidol University, Nakhon Pathom, Thailand.
authors.forename: Sutee
authors.initials: S
authors.lastname: Yoksan
authors.affiliation: Dengue Hemorrhagic Fever Research Unit Center for Emerging and Neglected Infectious Diseases Medical Biotechnology Research Unit, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Bangkok.
authors.forename: Prida
authors.initials: P
authors.lastname: Malasit
authors.affiliation: Interactions Moléculaires Flavivirus-Hôtes, Department of Virology, Institut Pasteur.
authors.forename: Philipe
authors.initials: P
authors.lastname: Despres
authors.affiliation: Unité de Génétique Fonctionnelle des Maladies Infectieuses, Department Genome and Genetics Centre National de la Recherche Scientifique, URA3012, Paris, France.
authors.forename: Richard
authors.initials: R
authors.lastname: Paul
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Nankang, Taiwan.
authors.forename: Yi-Ling
authors.initials: YL
authors.lastname: Lin
authors.affiliation: Unité de Génétique Fonctionnelle des Maladies Infectieuses, Department Genome and Genetics Centre National de la Recherche Scientifique, URA3012, Paris, France Systems Biology of Diseases Unit, Faculty of Science.
authors.forename: Anavaj
authors.initials: A
authors.lastname: Sakuntabhai
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics* / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D003715:Dengue / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D003716:Dengue Virus / Q000276:immunology*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D008297:Male; D055815:Young Adult
chemical_list: C475085:OAS1 protein, human; D015088:2',5'-Oligoadenylate Synthetase; C577439:OAS3 protein, human
keywords: cytokine storm; dengue virus; genetic susceptibility; innate immunity; interferon