@article{01JPAP526RX80XV0GJDPAHPK26,
  abstract     = {{Chan et al. report inherited DBR1 deficiency as a genetic etiology of isolated SARS-CoV-2 brainstem encephalitis. DBR1 I120T/I120T patient-specific hPSC-derived hindbrain neurons display enhanced accumulation of RNA lariats resulting in increased susceptibility to SARS-CoV-2 infection, thereby underlying SARS-CoV-2 brainstem encephalitis.

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.}},
  articleno    = {{e20231725}},
  author       = {{Chan, Yi-Hao and Lundberg, Vanja and Le Pen, Jérémie and Yuan, Jiayi and Lee, Danyel and Pinci, Francesca and Volpi, Stefano and Nakajima, Koji and Bondet, Vincent and Åkesson, Sanna and Khobrekar, Noopur V. and Bodansky, Aaron and Du, Likun and Melander, Tina and Mariaggi, Alice-Andrée and Seeleuthner, Yoann and Saleh, Tariq Shikh and Chakravarty, Debanjana and Marits, Per and Dobbs, Kerry and Vonlanthen, Sofie and Hennings, Viktoria and Thörn, Karolina and Rinchai, Darawan and Bizien, Lucy and Chaldebas, Matthieu and Sobh, Ali and Özçelik, Tayfun and Keles, Sevgi and AlKhater, Suzan A. and Prando, Carolina and Meyts, Isabelle and Bastard, Paul and Borghesi, Alessandro and Bousfiha, Aziz and Boyarchuk, Oksana and Brodin, Petter and Bustamante, Jacinta and Casari, Giorgio and Chevalier, Rémi and Christodoulou, John and Colobran, Roger and Condino-Neto, Antonio and Aldave Becerra, Juan Carlos and Arkin, Lisa and Andreakos, Evangelos and Thorball, Christian W. and Espinosa, Sara and Flores, Carlos and Geraldo, Amyrath and Halwani, Rabih and Hatipoğlu, Nevin and Melaiki, Brahim and Fellay, Jacques and Gagro, Alenka and Itan, Yuval and Jeewandara, Chandima and Haerynck, Filomeen and Mansouri, Davood and Naesens, Leslie and Ng, Lisa F.P. and Okamoto, Keisuke and Soler-Palacin, Pere and Renia, Laurent and Onofre, Aurora Pujol and Resnick, Igor B. and Franco Restrepo, José Luis and Rivière, Jacques G. and Scherbina, Anna and Šedivá, Anna and Seppänen, Mikko R.J. and Su, Helen and Tangye, Stuart G and Temel, Sehime G. and Tayoun, Ahmad Abou and Turvey, Stuart and Uddin, K.M. Furkan and van de Beek, Diederik and Le Voyer, Tom and Vinh, Donald C. and Zhang, Shen-Ying and Casanova, Jean-Laurent and Wilson, Michael R. and Rosain, Jérémie and Jouanguy, Emmanuelle and Aubart, Mélodie and Abel, Laurent and Mogensen, Trine H. and Pan-Hammarström, Qiang and Gao, Daxing and Duffy, Darragh and Cobat, Aurélie and Berg, Stefan and Notarangelo, Luigi D. and Harschnitz, Oliver and Rice, Charles M. and Studer, Lorenz and Casanova, Jean-Laurent and Ekwall, Olov and Zhang, Shen-Ying and COVID Human Genetic Effort, [missing]}},
  issn         = {{0022-1007}},
  journal      = {{JOURNAL OF EXPERIMENTAL MEDICINE}},
  keywords     = {{INFECTION,IMMUNITY,VARIANT,CELLS}},
  language     = {{eng}},
  number       = {{9}},
  pages        = {{22}},
  title        = {{SARS-CoV-2 brainstem encephalitis in human inherited DBR1 deficiency}},
  url          = {{http://doi.org/10.1084/jem.20231725}},
  volume       = {{221}},
  year         = {{2024}},
}

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