Varicella-zoster virus CNS vasculitis and RNA polymerase III gene mutation in identical twins

Neurology. Neuroimmunology and Neuroinflammation
Madalina Carter-TimofteTrine H Mogensen

Abstract

Deficiency in the cytosolic DNA sensor RNA Polymerase III (POL III) was recently described in children with severe varicella-zoster virus (VZV) infection in the CNS or lungs. Here, we describe a pair of monozygotic female twins, who both experienced severe recurrent CNS vasculitis caused by VZV reactivation. The clinical presentation and findings included recurrent episodes of headache, dizziness, and neurologic deficits, CSF with pleocytosis and intrathecal VZV antibody production, and MRI of the brain showing ischemic lesions. We performed whole-exome sequencing and identified a rare mutation in the POL III subunit POLR3F. Subsequently, antiviral responses in patient peripheral blood mononuclear cells (PBMCs) were examined and compared with healthy controls. The identified R50W POLR3F mutation is predicted by bioinformatics to be damaging, and when tested in functional assays, patient PBMCs exhibited impaired antiviral and inflammatory responses to the POL III agonist poly(dA:dT) and increased viral replication compared with controls. Altogether, these cases add genetic and immunologic evidence to the novel association between defects in sensing of AT-rich DNA present in the VZV genome and increased susceptibility to severe m...Continue Reading

References

Dec 20, 2002·Journal of Neurovirology·Donald H GildenBagher Forghani
Nov 1, 2011·American Journal of Human Genetics·Martine TétreaultGeneviève Bernard
Apr 29, 2015·The Journal of Infection·Christopher J A Duncan, Sophie Hambleton
Jan 29, 2016·Nature Methods·Yuval ItanJean-Laurent Casanova
Jan 1, 2015·Nature Reviews. Disease Primers·Anne A GershonKoichi Yamanishi
Apr 4, 2017·The Journal of Infectious Diseases·Manuela SironiAndrea Gori
Aug 8, 2017·The Journal of Clinical Investigation·Benson OgunjimiTrine H Mogensen

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Citations

Aug 30, 2019·Current Opinion in Pediatrics·Huie Jing, Helen C Su
Sep 13, 2019·Journal of Virology·Yang Zhao, John Karijolich
Nov 23, 2018·Neurology. Neuroimmunology and Neuroinflammation·Josep Dalmau
Feb 28, 2020·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Laura Krogh HerlinTrine H Mogensen
Nov 7, 2019·Current Opinion in Pediatrics·Huie Jing, Helen C Su
Jul 3, 2020·Genes & Development·Meghdad Yeganeh, Nouria Hernandez
Jun 27, 2020·BMJ Case Reports·Jessica Hyejin OhMuhammad Ghazanfar Husnain
Jun 5, 2020·Journal of Neurovirology·Peter Ge Kennedy, Trine H Mogensen
Jul 23, 2020·Frontiers in Immunology·Madalina Elena Carter-TimofteTrine H Mogensen
Dec 5, 2019·Frontiers in Immunology·Catherine F Hatton, Christopher J A Duncan
Aug 29, 2020·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Rahila AnsariJeffrey I Cohen
Dec 19, 2020·Nature Communications·Ewan Phillip RamsayAlessandro Vannini
Feb 25, 2021·Transcription·Nayef Jarrous, Alexander Rouvinski
May 29, 2021·Journal of Neurology·Marta BertaminoUNKNOWN in behalf of Gaslini Stroke Study Group
May 26, 2020·Seminars in Ultrasound, CT, and MR·Valerie L Jewells, Richard E Latchaw
May 12, 2021·The Journal of Infectious Diseases·Michelle M ThomsenTrine H Mogensen
Aug 17, 2021·Frontiers in Molecular Biosciences·Elisabeth LataMartin Teichmann
Oct 30, 2021·Cellular and Molecular Life Sciences : CMLS·Chunmei CaiChunfu Zheng
Oct 21, 2021·Current Opinion in Pediatrics·Yesim DemirdagJoyce E Yu

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Methods Mentioned

BETA
PCR

Software Mentioned

SIFT
PolyPhen

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