Age-related urinary excretion of BK polyomavirus by nonimmunocompromised individuals

Abstract

Two polyomaviruses, BK virus (BKV) and JC virus (JCV), are ubiquitous in the human population, generally infecting children asymptomatically and then persisting in renal tissue. It is generally thought that reactivation leads to productive infection for both viruses, with progeny shed in the urine. Several studies have shown that the rate of JC viruria increases with the age of the host, but a systematic approach to examine the shedding of BKV has not been developed. To elucidate the relationship between BK viruria and host age, we obtained urine from donors (healthy volunteers or nonimmunocompromised patients) who were divided into nine age groups, each containing 50 members. A high-sensitivity PCR was used to detect BKV and JCV DNA from urinary samples, and the specificity of amplification was confirmed by sequencing or restriction analysis of the amplified fragments. The rate of BK viruria was relatively low in subjects aged <30 years but gradually increased with age in subjects aged > or =30 years. However, BK viruria was less frequent than JC viruria in adults. The detected BKV isolates were classified into subtypes, and detection rates for individual subtypes were compared among age groups; this analysis showed that viruria of subtypes I (the most prevalent subtype) and IV (the second most prevalent subtype) occurred more frequently in older subjects. Therefore, our results reveal new aspects of BK viruria in nonimmunocompromised individuals.

FIG. 1.

Incidence of urinary excretion of polyomavirus DNA in various age groups. There were 50 individuals in each age group. a, P < 0.05 versus the 20- to 29-year-old group; b, P < 0.05 versus the 10- to 19-year-old group and P < 0.01 versus the 20- to 29-year-old group; c, P < 0.01 versus the 0- to 9-, 10- to 19-, 30- to 39-, and 40- to 49-year-old groups and P < 0.01 versus the 20- to 29-year-old group; d, P < 0.01 versus the 0- to 9-year-old group and P < 0.05 versus the 10- to 19-year-old group; e, P < 0.01 versus the 0- to 9- and 10- to 19-year-old groups; f, P < 0.01 versus the 0- to 9- and 10- to 19-year-old groups and P < 0.05 versus the 20- to 29-year-old group; g, P < 0.01 versus the 0- to 9-, 10- to 19-, and 20- to 29-year-old groups; h, P < 0.01 versus the 0- to 9-, 10- to 19-, and 20- to 29-year-old groups and P < 0.05 versus the 30- to 39-year-old group.

FIG. 2.

NJ phylogenetic tree classifying 119 BKV isolates into subtypes. The 287-bp typing sequences detected in the current study plus 22 reference sequences (indicated by asterisks) (10, 21) were used to reconstruct the NJ phylogenetic tree. The phylogenetic tree was visualized using the NJ plot program. Subtypes are indicated to the right of the tree. The numbers at the nodes are the BPs (%) obtained for 1,000 replicates (shown only for major nodes). a, 20-36, 20-40, 30-30, and 30-33; b, 50-04, 60-37, 70-10, 70-11, 70-12, 80-26, 80-29, and 80-40; c, 50-37, 70-47, 80-07, and 80-45; d, 10-35, 20-32, 30-05, 30-06, 40-08, 40-47, 50-09, 50-11, 50-13, 50-16, 50-35, 50-43, 50-44, 50-48, 60-34, 60-46, 70-20, 70-25, 70-32, 70-34, 70-45, 80-01, 80-18, 80-20, 80-25, 80-36, and 80-43; e, 10-14, 20-35, 20-38, 20-46, 30-19, 40-40, 40-46, 40-50, 60-32, 70-08, 70-23, 70-42, 70-46, 80-16, 80-22, 80-33, 80-34, and 80-35; f, 40-01, 60-13, 60-18, 60-23, 60-50, and 70-31; g, 00-08, 00-50, 10-19, 20-08, 30-38, 30-49, 50-29, 80-08, 80-37, and 80-41.