Inborn errors of OAS-RNase L in SARS-CoV-2-related multisystem inflammatory syndrome in children.
Danyel LeeJérémie Le PenAhmad YatimBeihua DongYann AquinoMasato OgishiRemi PescarmonaEstelle TalouarnDarawan RinchaiPeng ZhangMagali PerretZhiyong LiuIolanda Jordan-GarcíaŞefika Elmas BozdemirGülsüm İclal BayhanCamille BeaufilsLucy BizienAurelie BisiauxWei-Te LeiMilena HasanJie ChenChristina GaughanAbhishek AsthanaValentina LibriJoseph M LunaFabrice JaffréHans-Heinrich HoffmannEleftherios MichailidisMarion MoreewsYoann SeeleuthnerKaya BilguvarShrikant M ManeCarlos FloresYu ZhangAndrés Augusto AriasRasheed BaileyAgatha SchlüterBaptiste MilisavljevicBenedetta BigioTom Le VoyerMarie MaternaAdrian GervaisMarcela Moncada-VelezFrancesca PalaTomi LazarovRomain LevyAnna-Lena NeehusJérémie RosainJessica PeelYi-Hao ChanMarie-Paule MorinRosa Maria Pino-RamirezSerkan BelkayaLazaro LorenzoJordi AntónSelket DelafontaineJulie ToubianaFanny BajolleVictoria FumadóMarta L DeDiegoNadhira FidouhFlore RozenbergJordi Pérez TurShuibing ChenTodd EvansFrederic GeissmannPierre LebonSusan R WeissDamien BonnetXavier Duvalnull nullnull nullQiang Pan-HammarströmAnna M PlanasIsabelle MeytsFilomeen HaerynckAurora PujolSancho-Shimizu VanessaClifford L DalgardJacinta BustamanteAnne PuelStéphanie Boisson-DupuisBertrand BoissonTom ManiatisQian ZhangPaul BastardLuigi Daniele NotarangeloVivien BéziatRebeca Perez de DiegoCarlos Rodriguez-GallegoHelen C SuRichard P LiftonEmmanuelle JouanguyAurélie CobatLaia AlsinaSevgi KelesElie HaddadLaurent AbelAlexandre BelotLluis Quintana-MurciCharles M RiceRobert H SilvermanShen-Ying ZhangJean Laurent CasanovaPublished in: Science (New York, N.Y.) (2023)
Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of OAS1 , OAS2 , or RNASEL in five unrelated children with MIS-C. The cytosolic double-stranded RNA (dsRNA)-sensing OAS1 and OAS2 generate 2'-5'-linked oligoadenylates (2-5A) that activate the single-stranded RNA-degrading ribonuclease L (RNase L). Monocytic cell lines and primary myeloid cells with OAS1, OAS2, or RNase L deficiencies produce excessive amounts of inflammatory cytokines upon dsRNA or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stimulation. Exogenous 2-5A suppresses cytokine production in OAS1-deficient but not RNase L-deficient cells. Cytokine production in RNase L-deficient cells is impaired by MDA5 or RIG-I deficiency and abolished by mitochondrial antiviral-signaling protein (MAVS) deficiency. Recessive OAS-RNase L deficiencies in these patients unleash the production of SARS-CoV-2-triggered, MAVS-mediated inflammatory cytokines by mononuclear phagocytes, thereby underlying MIS-C.
Keyphrases
- sars cov
- respiratory syndrome coronavirus
- induced apoptosis
- cell cycle arrest
- young adults
- oxidative stress
- coronavirus disease
- end stage renal disease
- signaling pathway
- newly diagnosed
- chronic kidney disease
- ejection fraction
- emergency department
- bone marrow
- small molecule
- physical activity
- peritoneal dialysis
- body mass index
- smoking cessation