title: Astrovirus VA1/HMO-C: an increasingly recognized neurotropic pathogen in immunocompromised patients.
abstract: BACKGROUND
  An 18-month-old boy developed encephalopathy, for which extensive investigation failed to identify an etiology, 6 weeks after stem cell transplant. To exclude a potential infectious cause, we performed high-throughput RNA sequencing on brain biopsy.
  
  
  METHODS
  RNA-Seq was performed on an Illumina Miseq, generating 20 million paired-end reads. Nonhost data were checked for similarity to known organisms using BLASTx. The full viral genome was sequenced by primer walking.
  
  
  RESULTS
  We identified an astrovirus, HAstV-VA1/HMO-C-UK1(a), which was highly divergent from human astrovirus (HAstV 1-8) genotypes, but closely related to VA1/HMO-C astroviruses, including one recovered from a case of fatal encephalitis in an immunosuppressed child. The virus was detected in stool and serum, with highest levels in brain and cerebrospinal fluid (CSF). Immunohistochemistry of the brain biopsy showed positive neuronal staining. A survey of 680 stool and 349 CSF samples identified a related virus in the stool of another immunosuppressed child.
  
  
  CONCLUSIONS
  The discovery of HAstV-VA1/HMO-C-UK1(a) as the cause of encephalitis in this case provides further evidence that VA1/HMO-C viruses, unlike HAstV 1-8, are neuropathic, particularly in immunocompromised patients, and should be considered in the differential diagnosis of encephalopathy. With a turnaround from sample receipt to result of <1 week, we confirm that RNA-Seq presents a valuable diagnostic tool in unexplained encephalitis.
authors.affiliation: Virology Department, Great Ormond Street Hospital for Children NHS Foundation Trust NIHR Biomedical Research Centre, Great Ormond Street Hospital for Children NHS Foundation Trust and University College London.
authors.forename: Julianne R
authors.initials: JR
authors.lastname: Brown
authors.affiliation: UCL Genetics Institute, University College London.
authors.forename: Sofia
authors.initials: S
authors.lastname: Morfopoulou
authors.affiliation: Virology Department, Barts Health NHS Trust.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Hubb
authors.affiliation: UCL Genetics Institute, University College London.
authors.forename: Warren A
authors.initials: WA
authors.lastname: Emmett
authors.affiliation: Molecular and Cellular Immunology.
authors.forename: Winnie
authors.initials: W
authors.lastname: Ip
authors.affiliation: NIHR Biomedical Research Centre, Great Ormond Street Hospital for Children NHS Foundation Trust and University College London.
authors.forename: Divya
authors.initials: D
authors.lastname: Shah
authors.affiliation: Molecular Haematology and Cancer Biology Unit, Institute of Child Health, University College London.
authors.forename: Tony
authors.initials: T
authors.lastname: Brooks
authors.affiliation: Department of Histopathology, Great Ormond Street Hospital for Children NHS Foundation Trust Birth Defects Research Centre, Institute of Child Health, University College London, United Kingdom.
authors.forename: Simon M L
authors.initials: SM
authors.lastname: Paine
authors.affiliation: Department of Histopathology, Great Ormond Street Hospital for Children NHS Foundation Trust.
authors.forename: Glenn
authors.initials: G
authors.lastname: Anderson
authors.affiliation: NIHR Biomedical Research Centre, Great Ormond Street Hospital for Children NHS Foundation Trust and University College London.
authors.forename: Alex
authors.initials: A
authors.lastname: Virasami
authors.affiliation: Virology Department, Barts Health NHS Trust.
authors.forename: C Y William
authors.initials: CY
authors.lastname: Tong
authors.affiliation: Virology Department, Barts Health NHS Trust.
authors.forename: Duncan A
authors.initials: DA
authors.lastname: Clark
authors.affiliation: UCL Genetics Institute, University College London.
authors.forename: Vincent
authors.initials: V
authors.lastname: Plagnol
authors.affiliation: Department of Histopathology, Great Ormond Street Hospital for Children NHS Foundation Trust Birth Defects Research Centre, Institute of Child Health, University College London, United Kingdom.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Jacques
authors.affiliation: Molecular and Cellular Immunology.
authors.forename: Waseem
authors.initials: W
authors.lastname: Qasim
authors.affiliation: Molecular Haematology and Cancer Biology Unit, Institute of Child Health, University College London.
authors.forename: Mike
authors.initials: M
authors.lastname: Hubank
authors.affiliation: Virology Department, Great Ormond Street Hospital for Children NHS Foundation Trust Department of Infection and Immunity.
authors.forename: Judith
authors.initials: J
authors.lastname: Breuer
mesh_terms: D019350:Astroviridae Infections / Q000175:diagnosis / Q000473:pathology / Q000821:virology*; D001483:Base Sequence; D001706:Biopsy; D001921:Brain / Q000473:pathology* / Q000648:ultrastructure; D018792:Encephalitis, Viral / Q000175:diagnosis* / Q000473:pathology* / Q000821:virology; D005243:Feces / Q000821:virology; D016679:Genome, Viral; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D016867:Immunocompromised Host; D007223:Infant; D008297:Male; D001257:Mamastrovirus / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D010802:Phylogeny; D015995:Prevalence; D012367:RNA, Viral / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D017423:Sequence Analysis, RNA; D033581:Stem Cell Transplantation
chemical_list: D012367:RNA, Viral
keywords: RNASeq; astrovirus; deep sequencing; encephalopathy; pathogen discovery