Polyomavirus BK non-coding control region rearrangements in health and disease.
BACKGROUND
BK virus is an increasingly recognized pathogen in transplanted patients. DNA sequencing of this virus shows considerable genomic variability.


METHODS
To understand the clinical significance of rearrangements in the non-coding control region (NCCR) of BK virus (BKV), we report a meta-analysis of 507 sequences, including 40 sequences generated in our own laboratory, for associations between rearrangements and disease, tissue tropism, geographic origin, and viral genotype.


RESULTS
NCCR rearrangements were less frequent in (a) asymptomatic BKV viruria compared to patients viral nephropathy (1.7% vs. 22.5%), and (b) viral genotype 1 compared to other genotypes (2.4% vs. 11.2%). Rearrangements were commoner in malignancy (78.6%), and Norwegians (45.7%), and less common in East Indians (0%), and Japanese (4.3%). A surprising number of rearranged sequences were reported from mononuclear cells of healthy subjects, whereas most plasma sequences were archetypal. This difference could not be related to potential recombinase activity in lymphocytes, as consensus recombination signal sequences could not be found in the NCCR region.


CONCLUSIONS
NCCR rearrangements are neither required nor a sufficient condition to produce clinical disease. BKV nephropathy and hemorrhagic cystitis are not associated with any unique NCCR configuration or nucleotide sequence.
Sharma
Preety M
PM
Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
Gupta
Gaurav
G
Vats
Abhay
A
Shapiro
Ron
R
Randhawa
Parmjeet S
PS
D001739:BK Virus / Q000235:genetics*; D015967:Gene Expression Regulation, Viral; D005838:Genotype; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects; D027601:Polyomavirus Infections / Q000821:virology*; D014412:Tumor Virus Infections / Q000821:virology*