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

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Depledge, Daniel P 
Kundu, Samit 
Atkinson, Claire 
Brown, Julianne R 


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.



Adult, Aged, Aged, 80 and over, Child, Child, Preschool, Cohort Studies, Coinfection, Cytoplasmic Vesicles, DNA, Viral, Encephalitis, Varicella Zoster, Genetic Variation, Genome, Viral, Herpesvirus 3, Human, Humans, Middle Aged, Viral Load, Young Adult

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J Infect Dis

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Oxford University Press (OUP)
Action Medical research GN2424 This work was supported by a UK MRC New Investigator Award to D. P. D; UCL/UCLH BRC (J. B.); Action Medical Research (grant number GN2424 to C. J. H); Swedish Research Council (P. N. and T. B.). The work was also support by an NIHR Fellowship (grant number DRF-2013-06-168 to F. M.), the Meningitis Research Foundation (grant number 0904.0), an NIHR Programme Grant in Applied Research (grant number RP-PG-0108-10048 to T. S.), and the NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool.