Sars-Cov-2 Brainstem Encephalitis in Human Inherited Dbr1 Deficiency

Sars-Cov-2 Brainstem Encephalitis in Human Inherited Dbr1 Deficiency Publisher

Chan YH¹ ; Lundberg V^{2, 3} ; Le Pen J⁴ ; Yuan J⁵ ; Lee D^{1, 6, 7} ; Pinci F⁸ ; Volpi S^{9, 10} ; Nakajima K¹ ; Bondet V¹¹ ; Akesson S³ ; Khobrekar NV⁵ ; Bodansky A¹² ; Du L¹³ ; Melander T¹⁴ Show All Authors

Chan YH¹
Lundberg V^{2, 3}
Le Pen J⁴
Yuan J⁵
Lee D^{1, 6, 7}
Pinci F⁸
Volpi S^{9, 10}
Nakajima K¹
Bondet V¹¹
Akesson S³
Khobrekar NV⁵
Bodansky A¹²
Du L¹³
Melander T¹⁴
Mariaggi AA¹⁵
Seeleuthner Y^{6, 7}
Saleh TS¹⁶
Chakravarty D^{17, 18}
Marits P^{19, 20}
Dobbs K²¹
Vonlanthen S^{19, 20}
Hennings V^{2, 3}
Thorn K³
Rinchai D¹
Bizien L^{6, 7}
Chaldebas M¹
Sobh A²²
Ozcelik T²³
Keles S²⁴
Alkhater SA^{25, 26}
Prando C²⁷
Meyts I²⁸
Wilson MR^{17, 18}
Rosain J^{1, 6, 7}
Jouanguy E^{1, 6, 7}
Aubart M^{6, 7, 29}
Abel L^{1, 6, 7}
Mogensen TH³⁰
Panhammarstrom Q¹³
Gao D^{31, 32}
Duffy D¹¹
Cobat A^{6, 7}
Berg S²
Notarangelo LD²¹
Harschnitz O⁸
Rice CM⁴
Studer L⁵
Casanova JL^{1, 6, 7, 33, 98, 99}
Ekwall O^{2, 3}
Zhang SY^{1, 6, 7, 96}
Bastard P³⁵
Borghesi A^{36, 37}
Bousfiha A³⁸
Boyarchuk O³⁹
Brodin P⁴⁰
Bustamante J³⁵
Casari G⁴¹
Chevalier R³⁵
Christodoulou J⁴²
Colobran R⁴⁵
Condinoneto A⁴⁶
Aldave Becerra JC⁴⁷
Arkin L⁴⁸
Andreakos E⁴⁹
Thorball CW⁵⁰
Espinosa S⁵¹
Flores C^{52, 53, 54}
Geraldo A³⁵
Halwani R⁵⁵
Hatipoglu N⁵⁶
Melaiki B⁵⁷
Fellay J^{58, 59, 60}
Gagro A^{61, 100}
Itan Y⁶²
Jeewandara C⁶³
Haerynck F⁶⁴
Mansouri D^{65, 66, 67}
Naesens L⁶⁴
Ng LFP⁶⁸
Okamoto K⁶⁹
Soler Palacin P⁷⁰
Renia L^{71, 72, 73}
Onofre AP⁷⁴
Resnick IB^{77, 78}
Ranco Restrepo JLF⁷⁹
Riviere JG⁷⁰
Scherbina A⁸⁰
Sediva A⁸¹
Seppanen MRJ⁸²
Su H⁸³
Tangye SG^{84, 101}
Temel SG^{85, 86}
Tayoun AA^{87, 88}
Turvey S^{89, 90}
Furkan Uddin KM^{91, 92}
Van De Beek D⁹³
Le Voyer T³⁵
Vinh DC^{94, 95}

Show Affiliations

1. St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, United States
2. Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
3. Department of Rheumatology and Inflammation Research, Institute of Medicine, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
4. Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY, United States
5. The Center for Stem Cell Biology, Sloan Kettering Institute for Cancer Research, New York, NY, United States
6. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, Paris, France
7. Paris City University, Imagine Institute, Paris, France
8. Human Technopole, Viale Rita Levi-Montalcini, Milan, Italy
9. Rheumatology and Autoinflammatory Diseases, IRCCS Giannina Gaslini Institute, Genoa, Italy
10. Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy
11. Translational Immunology Unit, Institut Pasteur, Paris City University, Paris, France
12. Department of Pediatrics, Division of Critical Care, University of California San Francisco, San Francisco, CA, United States
13. Department of Medical Biochemistry and Biophysics, Division of Immunology, Karolinska Institutet, Stockholm, Sweden
14. Department of Pediatrics, Harnosand Hospital, Region Vasternorrland, Sundsvall, Sweden
15. Laboratory of Virology, Assistance Publique-Hopitaux de Paris (AP-HP), Cochin Hospital, Paris, France
16. Department of Pediatric Dentistry, Sundsvall, Region Vasternorrland, Sundsvall, Sweden
17. Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, United States
18. Department of Neurology, University of California, San Francisco, San Francisco, CA, United States
19. Department of Medicine, Huddinge, Hematology Unit, Therapeutic Immunology and Transfusion, Karolinska University Hospital, Stockholm, Sweden
20. Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
21. Division of Intramural Research, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States
22. Department of Pediatrics, Mansoura University Children’s Hospital, Faculty of Medicine, Mansoura University, Mansoura, Egypt
23. Department of Molecular Biology and Genetics, Bilkent University, Ankara, Turkey
24. Necmettin Erbakan University, Konya, Turkey
25. College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
26. Department of Pediatrics, King Fahad University Hospital, Al-Khobar, Saudi Arabia
27. Faculty of Pequeno Principe, Pesquisa Pele Pequeno Principe Institute, Curitiba, Brazil
28. Department of Pediatrics, University Hospitals Leuven, Laboratory for Inborn Errors of Immunity, KU Leuven, Leuven, Belgium
29. Department of Pediatric Neurology, Necker-Enfants Malades Hospital, AP-HP, Paris, France
30. Department of Biomedicine, Aarhus University, Aarhus, Denmark
31. Division of Life Science and Medicine, Department of General Surgery, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, China
32. Division of Life Sciences and Medicine, Institute of Immunology and the CAS Key Laboratory of Innate Immunity and Chronic Disease, University of Science and Technology of China, Hefei, China
33. Department of Pediatrics, Necker Hospital for Sick Children, AP-HP, Paris, France
34. Howard Hughes Medical Institute, New York, NY, United States
35. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U.1163, Necker Hospital for Sick Children, Paris Descartes University, Imagine Institute, Paris, France
36. Neonatal Intensive Care Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
37. Fellay lab, Ecole Polytechnique Federale de Lausanne (EPFL), Lausanne, Switzerland
38. Clinical Immunology Unit, Casablanca Children’s Hospital, Ibn Rochd Medical School, King Hassan II University, Casablanca, Morocco
39. Department of Children’s Diseases and Pediatric Surgery, I. Horbachevsky Ternopil National Medical University, Ukraine
40. Science for Life Laboratory, Dept of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden
41. Pediatric Immunohematology, San Raffaele Hospital, Salute San Raffaele University, Milano, Italy
42. Brain and Mitochondrial Research Group, Murdoch Children’s Research Institute
43. Department of Paediatrics, University of Melbourne
44. The Royal Children’s Hospital, Melbourne, Australia
45. Immunology Division, Genetics Department, Vall d’Hebron Research Institute, Vall d’Hebron Barcelona Hospital Campus, Universitat Autonoma de Barcelona, Catalonia, Barcelona, Spain
46. Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, SP, Sao Paulo, Brazil
47. Allergy and Clinical Immunology, Lima, Peru
48. University of Wisconsin School of Medicine, Madison, WI, United States
49. Laboratory of Immunobiology, Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece
50. Precision Medical Unit, Hospital Center of Vaudois University, Lausanne, Switzerland
51. Instituto Nacional de Pediatria (National Institute of Pediatrics), Mexico City, Mexico
52. Research Unit, Nuestra Senora de la Candelaria University Hospital, EU, Santa Cruz de Tenerife, Spain
53. Genomics Division, Institute of Technology and Renewable Energies (ITER), EU, Granadilla de Abona, Spain
54. CIBER Respiratory Diseases, Carlos III Health Institute, Madrid, Spain
55. College of Medicine, University of Shajah, Shajah, United Arab Emirates
56. Pediatric Infectious Diseases Unit, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
57. Division of Neurology, Department of Pediatrics, Prince Sultan Military Medical City, Neurology-University of Sousse-Tunisia, Riyadh, Saudi Arabia
58. School of Life Sciences, Ecole Polytechnique Federale de Lausanne, Lausanne, Switzerland
59. Precision Medicine Unit, Biomedical Data Sciences Center, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
60. Swiss Institute of Bioinformatics, Lausanne, Switzerland
61. Department of Paediatrics, University of Zagreb School of Medicine, Children’s Hospital Zagreb, Zagreb, Croatia
62. Icahn School of Medicine at Mount Sinai, New York, NY, United States
63. Allergy, Immunology and Cell Biology Unit, University of Sri Jayawardenapura, Sri Lanka
64. Primary Immunodeficiency Research Laboratory, Center for Primary Immunodeficiency Ghent, Ghent University Hospital, Ghent, Belgium
65. Department of Clinical Immunology and Infectious Diseases, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
66. The Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of, Tuberculosis and Lung Diseases (NRITLD), Masih Daneshvari Hospital, Shahid Beheshti, University of Medical Sciences, Tehran, Iran
67. Pediatric Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti, Iran
68. A*STAR Infectious Disease Laboratories, Agency for Science, Technology and Research, Singapore
69. Department of Pediatrics, Tokyo Medical and Dental University, Tokyo, Japan
70. Pediatric Infectious Diseases and Immunodeficiencies Unit, Vall d’Hebron Research Institute, Vall d’Hebron Barcelona Hospital Campus, Universitat Autonoma de Barcelona, Catalonia, Barcelona, Spain
71. A*STAR Infectious Disease Labortories, Agency for Science, Technology and Research, Singapore
72. Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
73. School of Biological Sciences, Nanyang. Technological University, Singapore
74. Neurometabolic Diseases Laboratory, IDIBELL–Hospital Duran I Reynals
75. and Catalan Institution for Research and Advanced Studies (ICREA), Catalonia, EU, Barcelona, Spain
76. CIBERER U759, ISCiii, Madrid, Spain
77. Department of Medical Genetics, Hematopoietic Stem Cell Research Lab, MU-Varna, Bulgaria
78. Hebrew University, Jerusalem, Israel
79. Group of Inborn Errors of Immunity (Primary Immunodeficiencies (IDPs), A Jeffrey Modell Diagnostic and Research Center, Department of Microbiology & Parasitology, School of Medicine, University of Antioquia, Medellin, Colombia
80. Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Moscow, Russian Federation
81. Department of Immunology, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic
82. HUS Helsinki University Hospital, Children and Adolescents, Rare Disease Center, and Inflammation Center, Adult Immunodeficiency Unit, Majakka, Helsinki, Finland
83. Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, NIAID, NIH, Bethesda, MD, United States
84. Garvan Institute of Medical Research, Darlinghurst, NSW, Australia
85. Department of Medical Genetics and Department of Histology and Embryology, Faculty of Medicine, Bursa Uludag University, Gorukle, Bursa, Turkey
86. Department of Translational Medicine, Health Sciences Institute, Bursa Uludag University, Gorukle, Bursa, Turkey
87. Genomics Center of Excellence, Al Jalila Children’s Specialty Hospital, Dubai, United Arab Emirates
88. Center for Genomic Discovery, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates
89. Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada
90. BC Children’s Hospital Research Institute, Vancouver, BC, Canada
91. Centre for Precision Therapeutics, Genetic and Genomic Medicine Centre, NeuroGen Children Healthcare, Dhaka, Bangladesh
92. Holy Family Red Crescent Medical College, Dhaka, Bangladesh
93. Amsterdam UMC, University of Amsterdam, Department of Neurology, Amsterdam Neuroscience, Amsterdam, Netherlands
94. Department of Medicine, Division of Infectious Diseases, McGill University Health Centre, Montreal, QC, Canada
95. Infectious Disease Susceptibility Program, Research Institute, McGill University Health Centre, Montreal, QC, Canada
96. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, EU, Paris, France
97. Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, United States
98. Necker Hospital for Sick Children and INSERM, EU, Paris, France
99. Rockefeller University and Howard Hughes Medical Institute, New York, NY, United States
100. Josip Juraj Strossmayer University of Osijek, Medical Faculty Osijek, Osijek, Croatia
101. St Vincent’s Clinical School, Faculty of Medicine, UNSW, Sydney, NSW, Australia

Source: Journal of Experimental Medicine Published:2024

Abstract

Inherited deficiency of the RNA lariat–debranching enzyme 1 (DBR1) is a rare etiology of brainstem viral encephalitis. The cellular basis of disease and the range of viral predisposition are unclear.We report inherited DBR1 deficiency in a 14-year-old boywho suffered from isolated SARS-CoV-2 brainstem encephalitis. The patient is homozygous for a previously reported hypomorphic and pathogenic DBR1 variant (I120T). Consistently, DBR1 I120T/I120T fibroblasts from affected individuals from this and another unrelated kindred have similarly low levels of DBR1 protein and high levels of RNA lariats. DBR1 I120T/I120T human pluripotent stem cell (hPSC)–derived hindbrain neurons are highly susceptible to SARS-CoV-2 infection. Exogenous WT DBR1 expression in DBR1 I120T/I120T fibroblasts and hindbrain neurons rescued the RNA lariat accumulation phenotype. Moreover, expression of exogenous RNA lariats, mimicking DBR1 deficiency, increased the susceptibility ofWT hindbrain neurons to SARS-CoV-2 infection. Inborn errors of DBR1 impair hindbrain neuron–intrinsic antiviral immunity, predisposing to viral infections of the brainstem, including that by SARS-CoV-2. © 2024 Chan et al.

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Style	Citing Format
MLA	Chan YH, et al.. "Sars-Cov-2 Brainstem Encephalitis in Human Inherited Dbr1 Deficiency." Journal of Experimental Medicine, vol. 221, no. 9, 2024, pp. -.
APA	Chan YH, Lundberg V, Le Pen J, Yuan J, Lee D, Pinci F, Volpi S, Nakajima K, Bondet V, Akesson S, Khobrekar NV, Bodansky A, Du L, Melander T, Mariaggi AA, Seeleuthner Y, Saleh TS, Chakravarty D, Marits P, ... Vinh DC (2024). Sars-Cov-2 Brainstem Encephalitis in Human Inherited Dbr1 Deficiency. Journal of Experimental Medicine, 221(9), -.
Chicago	Chan YH, Lundberg V, Le Pen J, Yuan J, Lee D, Pinci F, Volpi S, et al.. "Sars-Cov-2 Brainstem Encephalitis in Human Inherited Dbr1 Deficiency." Journal of Experimental Medicine 221, no. 9 (2024): -.
Harvard	Chan YH et al. (2024) 'Sars-Cov-2 Brainstem Encephalitis in Human Inherited Dbr1 Deficiency', Journal of Experimental Medicine, 221(9), pp. -.
Vancouver	Chan YH, Lundberg V, Le Pen J, Yuan J, Lee D, Pinci F, et al.. Sars-Cov-2 Brainstem Encephalitis in Human Inherited Dbr1 Deficiency. Journal of Experimental Medicine. 2024;221(9):-.
BibTex	@article{ author = {Chan YH and Lundberg V and Le Pen J and Yuan J and Lee D and Pinci F and Volpi S and Nakajima K and Bondet V and Akesson S and Khobrekar NV and Bodansky A and Du L and Melander T and Mariaggi AA and Seeleuthner Y and Saleh TS and Chakravarty D and Marits P and Dobbs K and Vonlanthen S and Hennings V and Thorn K and Rinchai D and Bizien L and Chaldebas M and Sobh A and Ozcelik T and Keles S and Alkhater SA and Prando C and Meyts I and Wilson MR and Rosain J and Jouanguy E and Aubart M and Abel L and Mogensen TH and Panhammarstrom Q and Gao D and Duffy D and Cobat A and Berg S and Notarangelo LD and Harschnitz O and Rice CM and Studer L and Casanova JL and Ekwall O and Zhang SY and Bastard P and Borghesi A and Bousfiha A and Boyarchuk O and Brodin P and Bustamante J and Casari G and Chevalier R and Christodoulou J and Colobran R and Condinoneto A and Aldave Becerra JC and Arkin L and Andreakos E and Thorball CW and Espinosa S and Flores C and Geraldo A and Halwani R and Hatipoglu N and Melaiki B and Fellay J and Gagro A and Itan Y and Jeewandara C and Haerynck F and Mansouri D and Naesens L and Ng LFP and Okamoto K and Soler Palacin P and Renia L and Onofre AP and Resnick IB and Ranco Restrepo JLF and Riviere JG and Scherbina A and Sediva A and Seppanen MRJ and Su H and Tangye SG and Temel SG and Tayoun AA and Turvey S and Furkan Uddin KM and Van De Beek D and Le Voyer T and Vinh DC}, title = {Sars-Cov-2 Brainstem Encephalitis in Human Inherited Dbr1 Deficiency}, journal = {Journal of Experimental Medicine}, volume = {221}, number = {9}, pages = {-}, year = {2024} }
RIS	TY - JOUR AU - Chan YH AU - Lundberg V AU - Le Pen J AU - Yuan J AU - Lee D AU - Pinci F AU - Volpi S AU - Nakajima K AU - Bondet V AU - Akesson S AU - Khobrekar NV AU - Bodansky A AU - Du L AU - Melander T AU - Mariaggi AA AU - Seeleuthner Y AU - Saleh TS AU - Chakravarty D AU - Marits P AU - Dobbs K AU - Vonlanthen S AU - Hennings V AU - Thorn K AU - Rinchai D AU - Bizien L AU - Chaldebas M AU - Sobh A AU - Ozcelik T AU - Keles S AU - Alkhater SA AU - Prando C AU - Meyts I AU - Wilson MR AU - Rosain J AU - Jouanguy E AU - Aubart M AU - Abel L AU - Mogensen TH AU - Panhammarstrom Q AU - Gao D AU - Duffy D AU - Cobat A AU - Berg S AU - Notarangelo LD AU - Harschnitz O AU - Rice CM AU - Studer L AU - Casanova JL AU - Ekwall O AU - Zhang SY AU - Bastard P AU - Borghesi A AU - Bousfiha A AU - Boyarchuk O AU - Brodin P AU - Bustamante J AU - Casari G AU - Chevalier R AU - Christodoulou J AU - Colobran R AU - Condinoneto A AU - Aldave Becerra JC AU - Arkin L AU - Andreakos E AU - Thorball CW AU - Espinosa S AU - Flores C AU - Geraldo A AU - Halwani R AU - Hatipoglu N AU - Melaiki B AU - Fellay J AU - Gagro A AU - Itan Y AU - Jeewandara C AU - Haerynck F AU - Mansouri D AU - Naesens L AU - Ng LFP AU - Okamoto K AU - Soler Palacin P AU - Renia L AU - Onofre AP AU - Resnick IB AU - Ranco Restrepo JLF AU - Riviere JG AU - Scherbina A AU - Sediva A AU - Seppanen MRJ AU - Su H AU - Tangye SG AU - Temel SG AU - Tayoun AA AU - Turvey S AU - Furkan Uddin KM AU - Van De Beek D AU - Le Voyer T AU - Vinh DC TI - Sars-Cov-2 Brainstem Encephalitis in Human Inherited Dbr1 Deficiency JO - Journal of Experimental Medicine VL - 221 IS - 9 SP - EP - PY - 2024 ER -

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