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High Viral Diversity and Mixed Infections in Cerebral Spinal Fluid from Cases of Varicella Zoster Virus Encephalitis

Journal article
Authors D. P. Depledge
J. Cudini
S. Kundu
C. Atkinson
J. R. Brown
T. Haque
C. J. Houldcroft
Evelyn S. Koay
F. McGill
R. Milne
T. Whitfield
J. W. Tang
G. Underhill
Tomas Bergström
Peter Norberg
R. Goldstein
T. Solomon
J. Breuer
Published in Journal of Infectious Diseases
Volume 218
Issue 10
Pages 1592-1601
ISSN 0022-1899
Publication year 2018
Published at Institute of Biomedicine
Institute of Biomedicine, Department of Infectious Medicine
Pages 1592-1601
Language en
Subject categories Infectious Medicine


Background. Varicella zoster virus (VZV) may cause encephalitis, both with and without rash. Here we investigate whether viruses recovered from the central nervous system (CNS; encephalitis or meningitis) differ genetically from those recovered from non-CNS samples. Methods. Enrichment-based deep sequencing of 45 VZV genomes from cerebral spinal fluid (CSF), plasma, bronchoalveolar lavage (BAL), and vesicles was carried out with samples collected from 34 patients with and without VZV infection of the CNS. Results. Viral sequences from multiple sites in the same patient were identical at the consensus level. Virus from vesicle fluid and CSF in cases of meningitis showed low-level diversity. By contrast, plasma, BAL, and encephalitis had higher numbers of variant alleles. Two CSF-encephalitis samples had high genetic diversity, with variant frequency patterns typical of mixed infections with different clades. Conclusions. Low viral genetic diversity in vesicle fluid is compatible with previous observations that VZV skin lesions arise from single or low numbers of virions. A similar result was observed in VZV from cases of VZV meningitis, a generally self-limiting infection. CSF from cases of encephalitis had higher diversity with evidence for mixed clade infections in 2 cases. We hypothesize that reactivation from multiple neurons may contribute to the pathogenesis of VZV encephalitis.

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