Quasispecies analysis of JC virus DNA present in urine of healthy subjects

PLoS One. 2013 Aug 15;8(8):e70950. doi: 10.1371/journal.pone.0070950. eCollection 2013.


JC virus is a human polyomavirus that infects the majority of people without apparent symptoms in healthy subjects and it is the causative agent of progressive multifocal leucoencephalopathy (PML), a disorder following lytic infection of oligodendrocytes that mainly manifests itself under immunosuppressive conditions. A hallmark for JC virus isolated from PML-brain is the presence of rearrangements in the non-coding control region (NCCR) interspersed between the early and late genes on the viral genome. Such rearrangements are believed to originate from the archetype JC virus which is shed in urine by healthy subjects and PML patients. We applied next generation sequencing to explore the non-coding control region variability in urine of healthy subjects in search for JC virus quasispecies and rearrangements reminiscent of PML. For 61 viral shedders (out of a total of 254 healthy subjects) non-coding control region DNA and VP1 (major capsid protein) coding sequences were initially obtained by Sanger sequencing. Deletions between 1 and 28 nucleotides long appeared in ∼24.5% of the NCCR sequences while insertions were only detected in ∼3.3% of the samples. 454 pyrosequencing was applied on a subset of 54 urine samples demonstrating the existence of JC virus quasispecies in four subjects (∼7.4%). Hence, our results indicate that JC virus DNA in urine is not always restricted to one unique virus variant, but can be a mixture of naturally occurring variants (quasispecies) reflecting the susceptibility of the non-coding control region for genomic rearrangements in healthy individuals. Our findings pave the way to explore the presence of viral quasispecies and the altered viral tropism that might go along with it as a potential risk factor for opportunistic secondary infections such as PML.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • DNA, Viral / urine*
  • Female
  • Humans
  • JC Virus / classification
  • JC Virus / genetics*
  • JC Virus / isolation & purification
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Phylogeny
  • Polyomavirus Infections / virology*
  • Reproducibility of Results
  • Viral Proteins / genetics
  • Young Adult


  • DNA, Viral
  • Viral Proteins

Associated data

  • GENBANK/HF955438
  • GENBANK/HF955439
  • GENBANK/HF955440
  • GENBANK/HF955441
  • GENBANK/HF955442
  • GENBANK/HF955443
  • GENBANK/HF955444
  • GENBANK/HF955445
  • GENBANK/HF955446
  • GENBANK/HF955447
  • GENBANK/HF955448
  • GENBANK/HF955449
  • GENBANK/HF955450
  • GENBANK/HF955451
  • GENBANK/HF955452
  • GENBANK/HF955453
  • GENBANK/HF955454
  • GENBANK/HF955455
  • GENBANK/HF955456
  • GENBANK/HF955457
  • GENBANK/HF955458
  • GENBANK/HF955459
  • GENBANK/HF955460
  • GENBANK/HF955461
  • GENBANK/HF955462
  • GENBANK/HF955463
  • GENBANK/HF955464
  • GENBANK/HF955465
  • GENBANK/HF955466
  • GENBANK/HF955467
  • GENBANK/HF955468
  • GENBANK/HF955469
  • GENBANK/HF955470
  • GENBANK/HF955471
  • GENBANK/HF955472
  • GENBANK/HF955473
  • GENBANK/HF955474
  • GENBANK/HF955475
  • GENBANK/HF955476
  • GENBANK/HF955477
  • GENBANK/HF955478
  • GENBANK/HF955479
  • GENBANK/HF955480
  • GENBANK/HF955481
  • GENBANK/HF955482
  • GENBANK/HF955483
  • GENBANK/HF955484
  • GENBANK/HF955485
  • GENBANK/HF955486
  • GENBANK/HF955487
  • GENBANK/HF955488
  • GENBANK/HF955489
  • GENBANK/HF955490
  • GENBANK/HF955491
  • GENBANK/HF955492
  • GENBANK/HF955493
  • GENBANK/HF955494
  • GENBANK/HF955495
  • GENBANK/HF955496
  • GENBANK/HF955497
  • GENBANK/HF955498

Grant support

This work was funded in part by the ‘Agentschap voor Innovatie door Wetenschap en Technologie’; http://www.iwt.be/; IWT-project nr 120480. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding was received for this study.