Human SNORA31 variations impair cortical neuron-intrinsic immunity to HSV-1 and underlie herpes simplex encephalitis

Autor: Zobaida Alsum, Soraya Boucherit, Lluis Quintana-Murci, Peng Zhang, Luigi D. Notarangelo, Joseph A. Church, Daxing Gao, Rabih Halwani, Lazaro Lorenzo, Thomas M. Carlile, Maria F. Rojas-Duran, Ahmed Aziz Bousfiha, Yuval Itan, Laurent Abel, Flore Rozenberg, Fabien G. Lafaille, Wendy V. Gilbert, Jean-Laurent Casanova, Vimel Rattina, Marc Tessier-Lavigne, Lorenz Studer, Trine H. Mogensen, Bastian Zimmer, Benoit Henry, Søren R. Paludan, Shen-Ying Zhang, Franck Rapaport, Gregory A. Smith, Saleh Al-Muhsen, Michael J. Ciancanelli, Gaspard Kerner, Jessica L. McAlpine, Kerry Dobbs, Madalina E. Carter-Timofte, Laura Marques, Oliver Harschnitz, Osefame Ewaleifoh, Mary Hasek, Dominik Paquet, Marc Tardieu, Naima Amenzoui, Yoon Seung Lee, Dylan Kwart
Přispěvatelé: Rockefeller University [New York], Memorial Sloane Kettering Cancer Center [New York], Laboratory of Human Genetics of Infectious Diseases (Necker Branch - INSERM U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Northwestern University Feinberg School of Medicine, Aarhus University Hospital, National Institutes of Health [Bethesda] (NIH), Yale University [New Haven], Service de Virologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Sharjah, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Ibn Rochd University Hospital of Casablanca, University Hassan II of Casablanca, Morocco., King Saud University [Riyadh] (KSU), Centro Hospitalar do Porto, University of Southern California (USC), Service de neurologie pédiatrique et maladies métaboliques, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Stanford University, This work was funded in part by the National Center for Advancing Translational Sciences, National Institutes of Health (NIH), Clinical and Translational Science Award program (grant nos. UL1TR000043 and UL1TR001866), NIH grants (nos. R01AI088364 to J.L.C. and S.Y.Z., R01NS072381 to J.-L.C. and S.-Y.Z. and R01GM101316 to W.G.), a grant from the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (no. ANR-10-LABX-62-IBEID to L.A.) and the French National Research Agency (ANR) under the ‘Investments for the future’ program (no. ANR-10-IAHU-01 to L.A.), the ANR grant IEIHSEER (no. ANR-14-CE14-0008-01 to S.-Y.Z.), the Lundbeck Foundation (grant no. R268-2016-3927 to S.R.P.), the Rockefeller University, INSERM, Paris Descartes University and the St Giles Foundation., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-14-CE14-0008,IEIHSEER,L'encéphalite Herpétique de l'enfant résulte de déficits héréditaires d'immunité contre l'HSV-1: une exception ou une règle?(2014), ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), Hôpital Cochin [AP-HP], Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Southern California [Los Angeles, CA, USA], Université Paris Diderot - Paris 7 (UPD7)-Hôpital Robert Debré-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Lafaille, F G, Harschnitz, O, Lee, Y S, Zhang, P, Hasek, M L, Kerner, G, Itan, Y, Ewaleifoh, O, Rapaport, F, Carlile, T M, Carter-Timofte, M E, Paquet, D, Dobbs, K, Zimmer, B, Gao, D, Rojas-Duran, M F, Kwart, D, Rattina, V, Ciancanelli, M J, McAlpine, J L, Lorenzo, L, Boucherit, S, Rozenberg, F, Halwani, R, Henry, B, Amenzoui, N, Alsum, Z, Marques, L, Church, J A, Al-Muhsen, S, Tardieu, M, Bousfiha, A A, Paludan, S R, Mogensen, T H, Quintana-Murci, L, Tessier-Lavigne, M, Smith, G A, Notarangelo, L D, Studer, L, Gilbert, W, Abel, L, Casanova, J L & Zhang, S Y 2019, ' Human SNORA31 variations impair cortical neuron-intrinsic immunity to HSV-1 and underlie herpes simplex encephalitis ', Nature Medicine, vol. 25, no. 12, pp. 1873-1884 . https://doi.org/10.1038/s41591-019-0672-3
Nature Medicine
Nature Medicine, 2019, 25 (12), pp.1873-1884. ⟨10.1038/s41591-019-0672-3⟩
Nature Medicine, Nature Publishing Group, 2019, 25 (12), pp.1873-1884. ⟨10.1038/s41591-019-0672-3⟩
Nature medicine
ISSN: 1078-8956
1744-7933
DOI: 10.1038/s41591-019-0672-3
Popis: International audience; Herpes simplex virus-1 (HSV-1) encephalitis (HSE) is typically sporadic. Inborn errors of TLR3- and DBR1-mediated central nervous system cell-intrinsic immunity can account for forebrain and brainstem HSE, respectively. We report five unrelated patients with forebrain HSE, each heterozygous for one of four rare variants of SNORA31, encoding a small nucleolar RNA of the H/ACA class that are predicted to direct the isomerization of uridine residues to pseudouridine in small nuclear RNA and ribosomal RNA. We show that CRISPR/Cas9-introduced bi- and monoallelic SNORA31 deletions render human pluripotent stem cell (hPSC)-derived cortical neurons susceptible to HSV-1. Accordingly, SNORA31-mutated patient hPSC-derived cortical neurons are susceptible to HSV-1, like those from TLR3- or STAT1-deficient patients. Exogenous interferon (IFN)-β renders SNORA31- and TLR3- but not STAT1-mutated neurons resistant to HSV-1. Finally, transcriptome analysis of SNORA31-mutated neurons revealed normal responses to TLR3 and IFN-α/β stimulation but abnormal responses to HSV-1. Human SNORA31 thus controls central nervous system neuron-intrinsic immunity to HSV-1 by a distinctive mechanism.
Databáze: OpenAIRE
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