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

Lafaille, Fabien G ; Harschnitz, Oliver ; Lee, Yoon Seung ; Zhang, Peng ; Hasek, Mary L ; Kerner, Gaspard ; Itan, Yuval ; Ewaleifoh, Osefame ; Rapaport, Franck ; Carlile, Thomas M ; Carter-Timofte, Madalina E ; Paquet, Dominik ; Dobbs, Kerry ; Zimmer, Bastian ; Gao, Daxing ; Rojas-Duran, Maria F ; Kwart, Dylan ; Rattina, Vimel ; Ciancanelli, Michael J ; McAlpine, Jessica L ; Lorenzo, Lazaro ; Boucherit, Soraya ; Rozenberg, Flore ; Halwani, Rabih ; Henry, Benoit ; Amenzoui, Naima ; Alsum, Zobaida ; Marques, Laura ; Church, Joseph A ; Al-Muhsen, Saleh ; Tardieu, Marc ; Bousfiha, Ahmed Aziz ; Paludan, Søren R ; Mogensen, Trine Hyrup ; Quintana-Murci, Lluis ; Tessier-Lavigne, Marc ; Smith, Gregory A ; Notarangelo, Luigi D ; Studer, Lorenz ; Gilbert, Wendy ; Abel, Laurent ; Casanova, Jean-Laurent ; Zhang, Shen-Ying

Nature Medicine, 2019-12, Vol.25 (12), p.1873-1884 [Periódico revisado por pares]

United States: Nature Publishing Group

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Título:
Human SNORA31 variations impair cortical neuron-intrinsic immunity to HSV-1 and underlie herpes simplex encephalitis
Autor: Lafaille, Fabien G ; Harschnitz, Oliver ; Lee, Yoon Seung ; Zhang, Peng ; Hasek, Mary L ; Kerner, Gaspard ; Itan, Yuval ; Ewaleifoh, Osefame ; Rapaport, Franck ; Carlile, Thomas M ; Carter-Timofte, Madalina E ; Paquet, Dominik ; Dobbs, Kerry ; Zimmer, Bastian ; Gao, Daxing ; Rojas-Duran, Maria F ; Kwart, Dylan ; Rattina, Vimel ; Ciancanelli, Michael J ; McAlpine, Jessica L ; Lorenzo, Lazaro ; Boucherit, Soraya ; Rozenberg, Flore ; Halwani, Rabih ; Henry, Benoit ; Amenzoui, Naima ; Alsum, Zobaida ; Marques, Laura ; Church, Joseph A ; Al-Muhsen, Saleh ; Tardieu, Marc ; Bousfiha, Ahmed Aziz ; Paludan, Søren R ; Mogensen, Trine Hyrup ; Quintana-Murci, Lluis ; Tessier-Lavigne, Marc ; Smith, Gregory A ; Notarangelo, Luigi D ; Studer, Lorenz ; Gilbert, Wendy ; Abel, Laurent ; Casanova, Jean-Laurent ; Zhang, Shen-Ying
Assuntos: Adult ; Brain stem ; Cellular immunity ; Central nervous system ; Central Nervous System - immunology ; Central Nervous System - virology ; Child, Preschool ; CRISPR ; Diagnosis ; Encephalitis ; Encephalitis, Herpes Simplex - genetics ; Encephalitis, Herpes Simplex - immunology ; Encephalitis, Herpes Simplex - pathology ; Encephalitis, Herpes Simplex - virology ; Female ; Forebrain ; Gene expression ; Genetic aspects ; Genetic Predisposition to Disease ; Genetic variation ; Genetics ; Health aspects ; Herpes simplex ; Herpes simplex encephalitis ; Herpes viruses ; Herpesvirus 1, Human - genetics ; Herpesvirus 1, Human - immunology ; Herpesvirus 1, Human - pathogenicity ; Human behavior ; Human genetics ; Human health and pathology ; Humans ; Immunity ; Immunity - genetics ; Infant ; Infectious diseases ; Interferon ; Isomerization ; Life Sciences ; Male ; Medical examination ; Metagenome - genetics ; Metagenome - immunology ; Middle Aged ; Nervous system ; Neurons ; Neurons - immunology ; Neurons - virology ; Nucleoli ; Pluripotency ; Prefrontal cortex ; RNA, Small Nucleolar - genetics ; RNA, Small Nucleolar - immunology ; rRNA ; snoRNA ; snRNA ; Stat1 protein ; Stem cells ; TLR3 protein ; Toll-like receptors ; Uridine ; Viruses ; α-Interferon
É parte de: Nature Medicine, 2019-12, Vol.25 (12), p.1873-1884
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
PMCID: PMC7376819
F.G.L., O.H., Y.S.L. performed the experiments and analyzed the data. M.L.H., O.E., T.C., M.E.C.-T., D.P., K.D., B.Z., D.G., M.F.R.-D., D.K., M.J.C., J.L.M., L.L., F.R., S.R.P., T.H.M., M.T.-L, G.A.S., L.D.N., L.S., W.G. performed the experiments. S.B. assisted with patient recruitment. R.H., B.H., N.A., Z.A., L.M., J.A.C., S.A.-M., M.T., A.A.B. contributed patient samples and collected clinical data. P.Z., G.K., Y.I., F.R., V.R., L.Q.-M., L.A. analyzed the data. J.-L.C. and S.-Y.Z. analyzed the data, supervised the research, and wrote the paper with the help of all co-authors.
Equal contribution
Author Contributions
Descrição: 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.
Editor: United States: Nature Publishing Group
Idioma: Inglês

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

United States: Nature Publishing Group

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