Related Experiment Videos
Typing of human polyomavirus JC virus on the basis of restriction fragment length polymorphisms
Abstract:
JC virus DNA clones from the urine of nonimmunosuppressed Japanese individuals regularly contain an archetypal regulatory sequence which may have generated various regulatory sequences of JC virus isolates from patients with progressive multifocal leukoencephalopathy (PML). In this study, we established 15 new clones from the urine of Dutch, German, and Taiwanese healthy volunteers and patients. Most of these clones contained regulatory sequences essentially identical to the archetypal regulatory sequence. These clones, along with two representative urine-derived clones in Japan and five clones from the brains of PML patients (four established in the United States and one established in Japan), were analyzed with a number of restriction enzymes. We found nine restriction fragment length polymorphisms by which all clones were classified into either of the two types, A and B. Type A contained only clones from the West, while type B contained some from the West and all from eastern Asia. Each type contained both urine-derived and PML-derived clones. Furthermore, there was a close relationship between some urine-derived clones and some PML-derived clones in restriction site mapping analysis. These findings support the adaptation hypothesis which has been postulated to explain the genesis of PML-type JC viruses.
Insights
JC virus (JCV) DNA in urine from healthy individuals often contains an archetypal regulatory sequence. This sequence may evolve into PML-type JCV found in patients with progressive multifocal leukoencephalopathy (PML).
Area of Science:
- Virology
- Molecular Biology
- Genetics
Background:
- JC virus (JCV) is a human polyomavirus.
- JCV DNA clones from urine of healthy individuals typically possess an archetypal regulatory sequence.
- This archetypal sequence is hypothesized to be a precursor to diverse regulatory sequences found in JCV isolates from progressive multifocal leukoencephalopathy (PML) patients.
Purpose of the Study:
- To investigate the origin and evolution of JCV regulatory sequences.
- To compare JCV regulatory sequences from urine of healthy individuals across different geographic locations with those from PML patients.
- To test the adaptation hypothesis for the genesis of PML-type JCV.
Main Methods:
- Isolation and characterization of 15 new JCV DNA clones from urine of healthy volunteers and patients in the Netherlands, Germany, and Taiwan.
- Analysis of these new clones, along with existing urine-derived and PML-brain-derived JCV clones, using restriction enzyme digestion.
- Classification of JCV clones into types A and B based on nine restriction fragment length polymorphisms and subsequent restriction site mapping.
Main Results:
- Most newly established urine-derived JCV clones exhibited regulatory sequences identical to the archetypal sequence.
- JCV clones were classified into two types, A and B, based on restriction fragment length polymorphisms.
- Type A clones were predominantly from Western countries, while Type B included clones from the West and all from East Asia.
- Both urine-derived and PML-derived clones were found in each type.
- Restriction site mapping revealed close relationships between certain urine-derived and PML-derived JCV clones.
Conclusions:
- The findings support the adaptation hypothesis for the development of PML-type JCV.
- JCV regulatory sequences in urine, particularly the archetypal form, may serve as a reservoir for generating pathogenic variants.
- Geographic origin influences JCV regulatory sequence types, suggesting host-pathogen interactions and viral adaptation play roles in JCV evolution.