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

Autor: Lafaille FG; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA., Harschnitz O; The Center for Stem Cell Biology, Sloan-Kettering Institute for Cancer Research, New York, NY, USA.; Developmental Biology Program, Sloan-Kettering Institute for Cancer Research, New York, NY, USA., Lee YS; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Necker Hospital for Sick Children, Paris, France.; Paris Descartes University, Imagine Institute, Paris, France., Zhang P; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA., Hasek ML; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA., Kerner G; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Necker Hospital for Sick Children, Paris, France.; Paris Descartes University, Imagine Institute, Paris, France., Itan Y; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.; The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Ewaleifoh O; Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Rapaport F; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA., Carlile TM; Biogen, Cambridge, MA, USA., Carter-Timofte ME; Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.; Department of Biomedicine, Aarhus University, Aarhus, Denmark., Paquet D; Laboratory of Brain Development and Repair, The Rockefeller University, New York, NY, USA.; Institute for Stroke and Dementia Research, University Hospital, LMU Munich, Munich, Germany.; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany., Dobbs K; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Zimmer B; The Center for Stem Cell Biology, Sloan-Kettering Institute for Cancer Research, New York, NY, USA.; Developmental Biology Program, Sloan-Kettering Institute for Cancer Research, New York, NY, USA., Gao D; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA., Rojas-Duran MF; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA., Kwart D; Laboratory of Brain Development and Repair, The Rockefeller University, New York, NY, USA., Rattina V; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Necker Hospital for Sick Children, Paris, France.; Paris Descartes University, Imagine Institute, Paris, France., Ciancanelli MJ; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA., McAlpine JL; The Center for Stem Cell Biology, Sloan-Kettering Institute for Cancer Research, New York, NY, USA.; Developmental Biology Program, Sloan-Kettering Institute for Cancer Research, New York, NY, USA., Lorenzo L; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Necker Hospital for Sick Children, Paris, France.; Paris Descartes University, Imagine Institute, Paris, France., Boucherit S; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Necker Hospital for Sick Children, Paris, France.; Paris Descartes University, Imagine Institute, Paris, France., Rozenberg F; Virology Department, Paris Descartes University, Sorbonne Paris Cité University, Welfare Services Paris Hospital, Hospital Group Paris Center University, Paris, France., Halwani R; Sharjah Institute for Medical Research (SIMR), Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates., Henry B; Department of Infectious Diseases, Pitié-Salpêtrière Hospital, Paris, France., Amenzoui N; Clinical Immunology Unit, Children's Ibn Rushd Hospital and Clinical Immunology Laboratory, Inflammation and Allergy LICIA, Faculty of Medicine and Pharmacy, Hassan Ii University, Casablanca, Morocco., Alsum Z; Immunology Research Laboratory, Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia., Marques L; Pediatric Department, Infectious Diseases and Immunodeficiencies Unit, Porto Hospital Center, Porto, Portugal., Church JA; Department of Pediatrics, Children's Hospital Los Angeles and Keck School of Medicine, University of Southern California, Los Angeles, CA, USA., Al-Muhsen S; Prince Naif Center for Immunology Research, King Saud University, Riyadh, Saudi Arabia., Tardieu M; South Paris University Hospital, Paris Hospital Welfare Services, Department of Pediatric Neurology, Paris, France., Bousfiha AA; Clinical Immunology Unit, Children's Ibn Rushd Hospital and Clinical Immunology Laboratory, Inflammation and Allergy LICIA, Faculty of Medicine and Pharmacy, Hassan Ii University, Casablanca, Morocco., Paludan SR; Department of Biomedicine, Aarhus University, Aarhus, Denmark., Mogensen TH; Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.; Department of Biomedicine, Aarhus University, Aarhus, Denmark.; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark., Quintana-Murci L; Unit of Human Evolutionary Genetics, CNRS UMR2000, Institut Pasteur, Paris, France., Tessier-Lavigne M; Biogen, Cambridge, MA, USA.; Department of Biology, Stanford University, Stanford, CA, USA., Smith GA; Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Notarangelo LD; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Studer L; The Center for Stem Cell Biology, Sloan-Kettering Institute for Cancer Research, New York, NY, USA.; Developmental Biology Program, Sloan-Kettering Institute for Cancer Research, New York, NY, USA., Gilbert W; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA., Abel L; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Necker Hospital for Sick Children, Paris, France.; Paris Descartes University, Imagine Institute, Paris, France., Casanova JL; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA. casanova@rockefeller.edu.; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Necker Hospital for Sick Children, Paris, France. casanova@rockefeller.edu.; Paris Descartes University, Imagine Institute, Paris, France. casanova@rockefeller.edu.; Pediatric Immuno-Hematology Unit, Necker Hospital for Sick Children, Paris, France. casanova@rockefeller.edu.; Howard Hughes Medical Institute, New York, NY, USA. casanova@rockefeller.edu., Zhang SY; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA. shzh289@rockefeller.edu.; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Necker Hospital for Sick Children, Paris, France. shzh289@rockefeller.edu.; Paris Descartes University, Imagine Institute, Paris, France. shzh289@rockefeller.edu.
Jazyk: angličtina
Zdroj: Nature medicine [Nat Med] 2019 Dec; Vol. 25 (12), pp. 1873-1884. Date of Electronic Publication: 2019 Dec 05.
DOI: 10.1038/s41591-019-0672-3
Abstrakt: 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: MEDLINE