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



Depledge, Daniel P, Cudini, Juliana, Kundu, Samit, Atkinson, Claire, Brown, Julianne R, Haque, Tanzina, Houldcroft, Charlotte J, Koay, Evelyn S, McGill, Fiona, Milne, Richard
et al (show 8 more authors) (2018) High Viral Diversity and Mixed Infections in Cerebral Spinal Fluid From Cases of Varicella Zoster Virus Encephalitis. Journal of Infectious Diseases, 218 (10). 1592 - 1601.

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Abstract

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.

Item Type: Article
Uncontrolled Keywords: varicella zoster virus, encephalitis, viral population, evolution, neurotropism, pathogenesis
Depositing User: Symplectic Admin
Date Deposited: 25 Jan 2019 09:17
Last Modified: 09 Jan 2021 04:30
DOI: 10.1093/infdis/jiy358
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3030557