No abstract

Although polyomavirus JC (JCV) is the proven pathogen of progressive multifocal leukoencephalopathy, the fatal demyelinating disease, this virus is ubiquitous as a usually harmless symbiote among human beings. JCV propagates in the adult kidney and excretes its progeny in urine, from which JCV DNA can readily be recovered. The main mode of transmission of JCV is from parents to children through long cohabitation. In this study, we collected a substantial number of urine samples from native inhabitants of 34 countries in Europe, Africa, and Asia. A 610-bp segment of JCV DNA was amplified from each urine sample, and its DNA sequence was determined. A worldwide phylogenetic tree subsequently constructed revealed the presence of nine subtypes including minor ones. Five subtypes (EU, Af2, B1, SC, and CY) occupied rather large territories that overlapped with each other at their boundaries. The entire Europe, northern Africa, and western Asia were the domain of EU, whereas the domain of Af2 included nearly all of Africa and southwestern Asia all the way to the northeastern edge of India. Partially overlapping domains in Asia were occupied by subtypes B1, SC, and CY. Of particular interest was the recovery of JCV subtypes in a pocket or pockets that were separated by great geographic distances from the main domains of those subtypes. Certain of these pockets can readily be explained by recent migrations of human populations carrying these subtypes. Overall, it appears that JCV genotyping promises to reveal previously unknown human migration routes: ancient as well as recent.

Urine specimens from 120 patients attending urologic clinics were screened by blot hybridization for the presence of a polyomavirus DNA. Detected viral DNA was then identified as BK or JC by fine restriction enzyme analysis. BK and JC viral DNA was found in 5 (4%) and 35 (29%) patients, respectively. Detection rates were compared among three age groups: 0-29, 30-59, and 60-89 years. Detection of JC viral DNA increased with age and reached the highest value (45%) in the group aged 60-89 years. For BK viral DNA a correlation between detection and age was not clear because the rate of detection was low, although the highest rate (9%) occurred in the oldest group. To confirm the active urinary excretion of polyomavirus DNA in older patients, urine specimens from 23 patients (60-90 years) treated at an internal medicine clinic were examined for viral DNA. BK and JC viral DNA were in 2 (9%) and 12 patients (52%), respectively. These results suggest that JC virus is frequently reactivated in older individuals.

We molecularly cloned JC polyomavirus DNAs from urine samples of eight nonimmunosuppressed patients and two healthy individuals. The cloned viral DNAs all contained an archetypal regulatory sequence from which various regulatory sequences of JC polyomavirus isolates derived from patients with progressive multifocal leukoencephalopathy could have evolved by deletion and amplification.

BK polyomavirus (BKV) is ubiquitous in the human population, infecting children without obvious symptoms, and persisting in the kidney in a latent state. In immunosuppressed patients, BKV is reactivated and excreted in urine. BKV isolates have been classified into four subtypes (I-IV) using either serological or genotyping methods. To elucidate the subtypes of BKV prevalent in Japan, the 287 bp typing region in the viral genome was PCR-amplified from urine samples of 45 renal transplant (RT) and 31 bone-marrow transplant (BMT) recipients. The amplified fragments were subjected to a phylogenetic or RFLP analysis to determine the subtypes of BKV isolates in urine samples. Subtypes I, II, III and IV were detected, respectively, in 70-80, 0, 2-3 and 10-20 % of the BKV-positive patients in both patient groups. This pattern of distribution was virtually identical to patterns previously demonstrated in England, Tanzania and the United States, suggesting that BKV subtypes are distributed similarly in various human populations. Furthermore, transcriptional control regions (TCRs) were PCR-amplified from the urine samples of 25 RT and 20 BMT recipients, and their nucleotide sequences were determined. The basic TCR structure (the so-called archetype configuration) was observed in most isolates belonging to subtypes I, III and IV (subtype II isolates were not available), albeit with several nucleotide substitutions and a few single-nucleotide deletions (or insertions). Only three TCRs carried extensive sequence rearrangements. Thus, it was concluded that the archetypal configuration of the BKV TCR has been conserved during the evolution of BKV.