BK polyomavirus with archetypal and rearranged non-coding control regions is present in cerebrospinal fluids from

Ana Bárcena-Panero1,2,3, Juan E Echevarría1,3, Marijke Van Ghelue4

  • 1Network of Biomedical Investigation Centres in Epidemiology and Public Health (CIBERESP), Barcelona, Spain.

Insights

BK polyomavirus (BKPyV) may cause central nervous system (CNS) infections. Rearranged non-coding control regions (NCCRs) in BKPyV strains were not definitively linked to neurotropism in this study.

Area of Science:

  • Virology
  • Neuroscience
  • Infectious Diseases

Background:

  • BK polyomavirus (BKPyV) is increasingly recognized as an opportunistic pathogen affecting the human central nervous system (CNS).
  • The specific viral strains and genetic factors, particularly within the non-coding control region (NCCR), that contribute to BKPyV neurotropism remain unclear.

Purpose of the Study:

  • To investigate the association between BKPyV strains, specifically their NCCR conformations, and neurotropism.
  • To determine if rearranged NCCR sequences are characteristic of BKPyV CNS infections.

Main Methods:

  • Analysis of BKPyV large T-antigen DNA in 2406 cerebrospinal fluid (CSF) samples from neurological patients.
  • Sequencing of the NCCR from BKPyV strains isolated from CSF, transplant recipients, and healthy individuals.
  • Functional assessment of promoter activity of archetypal and rearranged NCCR variants in cell transfection studies.

Main Results:

  • BKPyV large T-antigen DNA was detected in 20 neurological patients.
  • Archetypal NCCR conformations were most prevalent; however, six neurological patients had BKPyV with rearranged NCCRs.
  • Rearranged NCCR promoters exhibited significantly higher activity in vitro compared to archetypal promoters.
  • In two cases, CSF and serum viral strains had differing NCCR conformations, suggesting distinct origins.

Conclusions:

  • BKPyV NCCR rearrangements are not a definitive marker for neurotropism.
  • The CNS infection by BKPyV may not solely originate from the dissemination of rearranged NCCR strains from the bloodstream.

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