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

Brown, J. R. et al. (2015) Astrovirus VA1/HMO-C: an increasingly recognized neurotropic pathogen in immunocompromised patients. Clinical Infectious Diseases, 60(6), pp. 881-888. (doi: 10.1093/cid/ciu940) (PMID:25572899) (PMCID:PMC4345817)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Clark, Dr Duncan
Authors: Brown, J. R., Morfopoulou, S., Hubb, J., Emmett, W. A., Ip, W., Shah, D., Brooks, T., Paine, S. M.L., Anderson, G., Virasami, A., Tong, C.Y. W., Clark, D. A., Plagnol, V., Jacques, T. S., Qasim, W., Hubank, M., and Breuer, J.
College/School:College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:Clinical Infectious Diseases
Publisher:Oxford University Press
ISSN:1058-4838
ISSN (Online):1537-6591
Copyright Holders:Copyright © 2015 The Authors
First Published:First published in Clinical Infectious Diseases 60(6):881-888
Publisher Policy:Reproduced under a Creative Commons License

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