Link to Pubmed [PMID] – 34979561
Link to DOI – 10.1093/infdis/jiab639
Link to HAL - Pasteur – https://hal.archives-ouvertes.fr/pasteur-03509651
J. Infect. Dis.
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.
Conclusions : Long read deep sequencing shed light on emergence of neurotropic JCV populations in PML.
Figure 1. Circular phylogenetic tree of JC polyomavirus strains from patients with progressive multifocal leukoencephalopathy (PML) and controls. Maximum-likelihood phylogenetic tree generated by PhyML software, based on whole genome alignment (with the exception of noncoding control region) from 46 samples and 113 reference sequences obtained from GenBank (see Materials and Methods). Cases 1–32, PML patients; cases 33–37, controls. Abbreviations: C, cerebrospinal fluid, CB, cerebral biopsy; U, urine.