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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, and others. (2018) High Viral Diversity and Mixed Infections in Cerebral Spinal Fluid From Cases of Varicella Zoster Virus Encephalitis. The Journal of Infectious Diseases, 218 (10). pp. 1592-1601. ISSN 0022-1899. (doi:10.1093/infdis/jiy358) (KAR id:69866)



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.


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.


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.


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
DOI/Identification number: 10.1093/infdis/jiy358
Uncontrolled keywords: varicella zoster virus, encephalitis, viral population, evolution, neurotropism, pathogenesis
Subjects: Q Science > QR Microbiology
Divisions: Divisions > Division of Human and Social Sciences > School of Anthropology and Conservation
Depositing User: Samit Kundu
Date Deposited: 31 Oct 2018 16:29 UTC
Last Modified: 08 Dec 2022 23:19 UTC
Resource URI: (The current URI for this page, for reference purposes)

University of Kent Author Information

Kundu, Samit.

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