SARS-CoV-2 brainstem encephalitis in human inherited DBR1 deficiency-Reference-Cited by-同舟云学术

SARS-CoV-2 brainstem encephalitis in human inherited DBR1 deficiency

Published:2024-07-18 Issue:9 Volume:221 Page:
ISSN:0022-1007
Container-title:Journal of Experimental Medicine
language:en
Short-container-title:

Author:

Chan Yi-Hao¹^ORCID,Lundberg Vanja²³^ORCID,Le Pen Jérémie⁴^ORCID,Yuan Jiayi⁵^ORCID,Lee Danyel¹⁶⁷^ORCID,Pinci Francesca⁸^ORCID,Volpi Stefano⁹¹⁰^ORCID,Nakajima Koji¹^ORCID,Bondet Vincent¹¹^ORCID,Åkesson Sanna³^ORCID,Khobrekar Noopur V.⁵^ORCID,Bodansky Aaron¹²^ORCID,Du Likun¹³^ORCID,Melander Tina¹⁴^ORCID,Mariaggi Alice-Andrée¹⁵^ORCID,Seeleuthner Yoann⁶⁷^ORCID,Saleh Tariq Shikh¹⁶^ORCID,Chakravarty Debanjana¹⁷¹⁸^ORCID,Marits Per¹⁹²⁰^ORCID,Dobbs Kerry²¹^ORCID,Vonlanthen Sofie¹⁹²⁰^ORCID,Hennings Viktoria²³^ORCID,Thörn Karolina³^ORCID,Rinchai Darawan¹^ORCID,Bizien Lucy⁶⁷^ORCID,Chaldebas Matthieu¹^ORCID,Sobh Ali²²^ORCID,Özçelik Tayfun²³^ORCID,Keles Sevgi²⁴^ORCID,AlKhater Suzan A.²⁵²⁶^ORCID,Prando Carolina²⁷^ORCID,Meyts Isabelle²⁸^ORCID,Bastard Paul,Borghesi Alessandro,Bousfiha Aziz,Boyarchuk Oksana,Brodin Petter,Bustamante Jacinta,Casari Giorgio,Chevalier Rémi,Christodoulou John,Colobran Roger,Condino-Neto Antonio,Aldave Becerra Juan Carlos,Arkin Lisa,Andreakos Evangelos,Thorball Christian W.,Espinosa Sara,Flores Carlos,Geraldo Amyrath,Halwani Rabih,Hatipoğlu Nevin,Melaiki Brahim,Fellay Jacques,Gagro Alenka,Itan Yuval,Jeewandara Chandima,Haerynck Filomeen,Mansouri Davood,Naesens Leslie,Ng Lisa F.P.,Okamoto Keisuke,Soler-Palacin Pere,Renia Laurent,Onofre Aurora Pujol,Resnick Igor B.,Franco Restrepo José Luis,Rivière Jacques G.,Scherbina Anna,Šedivá Anna,Seppänen Mikko R.J.,Su Helen,Tangye Stuart G,Temel Sehime G.,Tayoun Ahmad Abou,Turvey Stuart,Uddin K.M. Furkan,van de Beek Diederik,Le Voyer Tom,Vinh Donald C.,Zhang Shen-Ying,Casanova Jean-Laurent,Wilson Michael R.¹⁷¹⁸^ORCID,Rosain Jérémie¹⁶⁷^ORCID,Jouanguy Emmanuelle¹⁶⁷^ORCID,Aubart Mélodie⁶⁷²⁹^ORCID,Abel Laurent¹⁶⁷^ORCID,Mogensen Trine H.³⁰^ORCID,Pan-Hammarström Qiang¹³^ORCID,Gao Daxing³¹³²,Duffy Darragh¹¹^ORCID,Cobat Aurélie⁶⁷^ORCID,Berg Stefan²^ORCID,Notarangelo Luigi D.²¹^ORCID,Harschnitz Oliver⁸^ORCID,Rice Charles M.⁴^ORCID,Studer Lorenz⁵^ORCID,Casanova Jean-Laurent¹⁶⁷³³³⁴^ORCID,Ekwall Olov²³^ORCID,Zhang Shen-Ying¹⁶⁷^ORCID,

Affiliation:

1. St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University 1 , New York, NY, USA

2. Institute of Clinical Sciences, The Sahlgrenska Academy at the University of Gothenburg 2 Department of Pediatrics, , Gothenburg, Sweden

3. Institute of Medicine, The Sahlgrenska Academy at the University of Gothenburg 3 Department of Rheumatology and Inflammation Research, , Gothenburg, Sweden

4. The Rockefeller University 4 Laboratory of Virology and Infectious Disease, , New York, NY, USA

5. The Center for Stem Cell Biology, Sloan Kettering Institute for Cancer Research 5 , New York, NY, USA

6. Necker Branch, INSERM 6 Laboratory of Human Genetics of Infectious Diseases, , Paris, France

7. Paris City University, Imagine Institute 7 , Paris, France

8. Human Technopole, Viale Rita Levi-Montalcini 8 , Milan, Italy

9. IRCCS Giannina Gaslini Institute 9 Rheumatology and Autoinflammatory Diseases, , Genoa, Italy

10. Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa 10 Department of Neuroscience, , Genoa, Italy

11. Translational Immunology Unit, Institut Pasteur, Paris City University 11 , Paris, France

12. University of California San Francisco 12 Department of Pediatrics, Division of Critical Care, , San Francisco, CA, USA

13. Karolinska Institutet 13 Department of Medical Biochemistry and Biophysics, Division of Immunology, , Stockholm, Sweden

14. Härnösand Hospital, Region Västernorrland 14 Department of Pediatrics, , Sundsvall, Sweden

15. Laboratory of Virology, Assistance Publique-Hôpitaux de Paris (AP-HP), Cochin Hospital 15 , Paris, France

16. Sundsvall, Region Västernorrland 16 Department of Pediatric Dentistry, , Sundsvall, Sweden

17. Weill Institute for Neurosciences, University of California, San Francisco 17 , San Francisco, CA, USA

18. University of California, San Francisco 18 Department of Neurology, , San Francisco, CA, USA

19. Huddinge, Hematology Unit, Therapeutic Immunology and Transfusion, Karolinska University Hospital 19 Department of Medicine, , Stockholm, Sweden

20. Intervention and Technology, Karolinska Institutet 20 Department of Clinical Science, , Stockholm, Sweden

21. Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health 21 Division of Intramural Research, , Bethesda, MD, USA

22. Mansoura University Children’s Hospital, Faculty of Medicine, Mansoura University 22 Department of Pediatrics, , Mansoura, Egypt

23. Bilkent University 23 Department of Molecular Biology and Genetics, , Ankara, Turkey

24. Necmettin Erbakan University 24 , Konya, Turkey

25. College of Medicine, Imam Abdulrahman Bin Faisal University 25 , Dammam, Saudi Arabia

26. King Fahad University Hospital 26 Department of Pediatrics, , Al-Khobar, Saudi Arabia

27. Faculty of Pequeno Príncipe, Pesquisa Pelé Pequeno Príncipe Institute 27 , Curitiba, Brazil

28. University Hospitals Leuven, Laboratory for Inborn Errors of Immunity, KU Leuven 28 Department of Pediatrics, , Leuven, Belgium

29. Necker-Enfants Malades Hospital, AP-HP 29 Department of Pediatric Neurology, , Paris, France

30. Aarhus University 30 Department of Biomedicine, , Aarhus, Denmark

31. The First Affiliated Hospital of USTC, University of Science and Technology of China 31 Division of Life Science and Medicine, Department of General Surgery, , Hefei, China

32. Institute of Immunology and the CAS Key Laboratory of Innate Immunity and Chronic Disease, University of Science and Technology of China 32 Division of Life Sciences and Medicine, , Hefei, China

33. Necker Hospital for Sick Children, AP-HP 33 Department of Pediatrics, , Paris, France

34. Howard Hughes Medical Institute 34 , New York, NY, USA

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 boy who 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 of WT 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.

Publisher

Rockefeller University Press

Link

https://rupress.org/jem/article-pdf/doi/10.1084/jem.20231725/1930725/jem_20231725.pdf

Reference35 articles.

1. Neuroinflammatory disease following severe acute respiratory syndrome coronavirus 2 infection in children;Aubart;J. Pediatr.,2022

2. Autoantibodies neutralizing type I IFNs are present in ∼4% of uninfected individuals over 70 years old and account for ∼20% of COVID-19 deaths;Bastard;Sci. Immunol.,2021

3. Herpes simplex encephalitis in a patient with a distinctive form of inherited IFNAR1 deficiency;Bastard;J. Clin. Invest.,2021

4. From rare disorders of immunity to common determinants of infection: Following the mechanistic thread;Casanova;Cell,2022

5. Mechanisms of viral inflammation and disease in humans;Casanova;Science,2021