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Clin Infect Dis. 2015 Mar 15;60(6):881-8. doi: 10.1093/cid/ciu940. Epub 2015 Jan 7.

Astrovirus VA1/HMO-C: an increasingly recognized neurotropic pathogen in immunocompromised patients.

Author information

1
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.
2
UCL Genetics Institute, University College London.
3
Virology Department, Barts Health NHS Trust.
4
Molecular and Cellular Immunology.
5
NIHR Biomedical Research Centre, Great Ormond Street Hospital for Children NHS Foundation Trust and University College London.
6
Molecular Haematology and Cancer Biology Unit, Institute of Child Health, University College London.
7
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.
8
Department of Histopathology, Great Ormond Street Hospital for Children NHS Foundation Trust.
9
Virology Department, Great Ormond Street Hospital for Children NHS Foundation Trust Department of Infection and Immunity.

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.

KEYWORDS:

RNASeq; astrovirus; deep sequencing; encephalopathy; pathogen discovery

PMID:
25572899
PMCID:
PMC4345817
DOI:
10.1093/cid/ciu940
[Indexed for MEDLINE]
Free PMC Article

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