Mary Wilson
Well-known member
20 Dec 2022
First Release
DOI: 10.1126/science.abo3627
DANYEL LEE, JÉRÉMIE LE PEN, AHMAD YATIM, BEIHUA DONG, YANN AQUINO, MASATO OGISHI, RÉMI PESCARMONA, ESTELLE TALOUARN, DARAWAN RINCHAI, [...], AND JEAN-LAURENT CASANOVA +94 authors
Abstract
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 dsRNA-sensing OAS1 and OAS2 generate 2′-5′-linked oligoadenylates (2-5A) that activate the ssRNA-degrading RNase L. Monocytic cell lines and primary myeloid cells with OAS1, OAS2, or RNASEL deficiencies produce excessive amounts of inflammatory cytokines upon dsRNA or SARS-CoV-2 stimulation. Exogenous 2-5A suppresses cytokine production in OAS1- but not RNase L-deficient cells. Cytokine production in RNase L-deficient cells is impaired by MDA5 or RIG-I deficiency and abolished by 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.
https://www.science.org/doi/10.1126/science.abo3627#.Y6JrPeqnN5Y.twitter
First Release
DOI: 10.1126/science.abo3627
DANYEL LEE, JÉRÉMIE LE PEN, AHMAD YATIM, BEIHUA DONG, YANN AQUINO, MASATO OGISHI, RÉMI PESCARMONA, ESTELLE TALOUARN, DARAWAN RINCHAI, [...], AND JEAN-LAURENT CASANOVA +94 authors
Abstract
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 dsRNA-sensing OAS1 and OAS2 generate 2′-5′-linked oligoadenylates (2-5A) that activate the ssRNA-degrading RNase L. Monocytic cell lines and primary myeloid cells with OAS1, OAS2, or RNASEL deficiencies produce excessive amounts of inflammatory cytokines upon dsRNA or SARS-CoV-2 stimulation. Exogenous 2-5A suppresses cytokine production in OAS1- but not RNase L-deficient cells. Cytokine production in RNase L-deficient cells is impaired by MDA5 or RIG-I deficiency and abolished by 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.
https://www.science.org/doi/10.1126/science.abo3627#.Y6JrPeqnN5Y.twitter