JC Polyomavirus whole genome sequencing at the single molecule level reveals emerging neurotropic populations in Progressive Multifocal Leucoencephalopathy

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L’honneur, Anne-Sophie | Pipoli da Fonseca, Juliana | Cokelaer, Thomas | Rozenberg, Flore

Edité par CCSD ; Oxford University Press -

International audience. Background JC polyomavirus (JCV) mostly causes asymptomatic persistent renal infections but may give rise in immunosuppressed patients to neurotropic variants which replicate in the brain causing progressive multifocal leukoencephalopathy (PML). Rearrangements in the JCV genome regulator non-coding control region (NCCR) and missense mutations in the viral capsid VP1 gene differentiate neurotropic variants from virus excreted in urine. Methods To investigate intra-host emergence of JCV neurotropic populations in PML, we deep sequenced JCV whole genome recovered from cerebrospinal fluid (CSF) and urine samples from 32 HIV- and non HIV-infected PML patients at the single-molecule level. Results JCV strains distributed among 6 out of 7 known genotypes. Common patterns of NCCR rearrangements included an initial deletion mostly located in a short 10-nucleotide sequence, followed by duplications/insertions. Multiple NCCR variants present in individual CSF samples shared at least one rearrangement suggesting they stemmed from a unique viral population. NCCR variants independently acquired single or double PML-specific adaptive VP1 mutations. NCCR variants recovered from urine and CSF displayed opposite deletion or duplication patterns in binding sites for transcription factors. Discussion Long read deep sequencing shed light on emergence of neurotropic JCV populations in PML.

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