Inborn errors of OAS–RNase L in SARS-CoV-2–related multisystem inflammatory syndrome in children

DOI HANDLE HANDLE HANDLE HANDLE ほか6件をすべて表示 一部だけ表示 研究データあり 被引用文献3件 参考文献1件 オープンアクセス

書誌事項

公開日
2023-02-10
DOI
  • 10.1126/science.abo3627
公開者
American Association for the Advancement of Science (AAAS)

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説明

<jats:p> Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of <jats:italic>OAS1</jats:italic> , <jats:italic>OAS2</jats:italic> , or <jats:italic>RNASEL</jats:italic> 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. </jats:p>

収録刊行物

  • Science

    Science 379 (6632), eabo3627-, 2023-02-10

    American Association for the Advancement of Science (AAAS)

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