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 >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.Humans are infected with two polyomaviruses, JC virus (JCV) and BK virus (BKV), and serological surveys have shown that both viruses are ubiquitous in the human population, generally infecting children asymptomatically (18) and then persisting in renal tissue (4, 7). Both viruses are usually nonpathogenic for nonimmunocompromised individuals, but they cause clinically significant diseases in immunocompromised patients. Thus, BKV causes BKV-associated nephropathy in organ transplant patients (e.g., renal transplant patients) (8), while JCV causes progressive multifocal leukoencephalopathy, typically in patients infected with human immunodeficiency virus (2).Renal JCV and BKV in nonimmunocompromised individuals are not latent but replicate frequently, excreting progeny viruses in urine. The incidence of JC viruria is known to increase with age and reaches nearly 70% at 80 to 89 years old (12, 13); in contrast, the shedding of BKV has not been studied systematically (15), although it is likely that BK viruria is also age dependent. To establish the relationship between BK viruria and host age, we collected urine samples from nonimmunocompromised individuals (healthy volunteers and general patients, all of whom were Japanese). The urine donors were divided into nine groups based on age (0 to 9, 10 to 19, 20 to 29, 30 to 39, 40 to 49, 50 to 59, 60 to 69, 70 to 79, and 80 to 89 years old), with each group having 50 members. A high-sensitivity PCR was used to detect BKV DNA from urinary samples, and the specificity of amplification was confirmed by sequencing of the amplified frag...

BK Polyomavirus Genotypes Represent Distinct Serotypes with Distinct Entry Tropism

“…The virus is thought to establish a lifelong chronic infection in the urinary epithelium, and virions are periodically shed at low levels in the urine of 5 to 27% of healthy adults (4,5). Although BKV-I can cause malignancy in animal model systems, conclusive evidence showing a causal connection between BKVs and human cancer is still lacking (reviewed in reference 6).…”

Pretransplantation Donor–Recipient Pair Seroreactivity Against BK Polyomavirus Predicts Viremia and Nephropathy After Kidney Transplantation

“…After primary infection, BKPyV latently persists in the urothelium and renal tubular cells (5,6), and small amounts of viral progeny can be temporarily detected in urine of 7-55% of healthy persons, depending on the sampling frequency (7)(8)(9).…”

Occurrence of the European Subgroup of Subtype I BK Polyomavirus in Japanese-Americans Suggests Transmission outside the Family

“…Since BKV is also frequently detected in the urine of immunocompetent individuals (27), the methods used to clarify the mode of JCV transmission should be applicable to BKV. To test the hypothesis that, similar to JCV, BKV is transmitted within the family, here we used urine samples previously collected from Japanese-Americans for the study of JCV transmission (18).…”

“…Renal BKV in immunocompetent individuals is not latent but replicates frequently, and progeny viruses are excreted in urine (27). In immunosuppressed patients (particularly renal transplant recipients), BKV may cause renal dysfunction such as BKV-associated nephropathy (6).…”