Summary auto-generated
JC virus (JCV) causes progressive multifocal leukoencephalopathy (PML), a demyelinating disease affecting the central nervous system. This study examined 29 JCV strains from brain or cerebrospinal fluid samples of PML patients to characterize regulatory region rearrangements and viral genotypes. The researchers found that JCV strains in urine have a standard 267-nucleotide regulatory region, while PML tissue strains show unique rearrangements involving deletions and duplications. Analysis revealed that regulatory region rearrangements occur independently of viral genotypes (Types 1-4), which are distinguished by coding region variations. Among the 29 PML strains, Types 1 and 2 were equally prevalent at 48% each, contrasting with urine samples where Type 1 dominates at 65%. All rearranged regulatory regions were unique, yet each could be derived from the archetypal form. The most common rearrangement pattern involved deletion of the central region with duplication of flanking areas. Critically, certain regulatory elements like the TATA box and first NF-1 binding site were preserved across all strains, indicating functional constraints. The findings demonstrate that regulatory region rearrangements and genotypes represent independent aspects of JCV variation, and the lack of association suggests additional genomic factors determine viral pathogenicity.
Key findings
- Regulatory region rearrangements in PML-derived JCV strains are completely independent of viral genotypes (Types 1-4)
- All 29 examined PML strains showed unique regulatory region configurations, yet each derived from a single archetypal 267-bp form through deletions and duplications
- Essential regulatory elements including the TATA box and first NF-1 binding site are preserved in all PML strains despite extensive rearrangements
- JCV Type 2 is overrepresented in PML tissue (48%) compared to urinary samples (15-20%), suggesting genotype-specific pathogenic behavior
- The most common rearrangement pattern involves deletion of the central regulatory region (bp 115-180) with flanking duplications
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Abstract
JC virus (JCV) causes the central demyelinating disease progressive multifocal leukoencephalopathy (PML). JCV strains excreted in the urine are distinguishable from those in PML tissue by the configuration of their regulatory region to the right of ori: the archetypal regulatory region, 267 nucleotides long, is rearranged in PML tissue by deletion and duplication. Within the coding region JCV shows variations as a result of virus evolution. Four major genotypes are distinguishable of which Type 1 is based in Europe and Type 2 in Asia. Here, the regulatory region rearrangements and the viral genotypes of 29 JCV strains from PML brain were determined. Rearrangement patterns and genotypes were not associated. In general, deletions occurred before duplications, but exceptions to this rule exist. Each configuration of the 29 rearranged regulatory regions was unique and could be derived directly from the non-rearranged, archetypal form.