Noncoding Control Region Pattern of BK polyomavirus in Kidney Transplant Patients With Nephropathy

摘要

Objectives: Adaptation of BK polyomavirus with infected host cells may cause rearrangement of the noncoding control region of viral genomic DNA. Archetype, the prearranged transmissible form of the virus, actively replicates in the tubular epithelial cells, whereas isolates with rearranged noncoding control region sequences are found in other parts of the kidney. Clinical observations highlighted the importance of the noncoding control region rearrangements in BK virus-associated nephropathy. Therefore, we evaluated the sequence pattern of the noncoding control region in kidney transplant patients suspected of having BK virus-associated nephropathy. Materials and Methods: In this single-center, cross-sectional study, 129 kidney transplant patients suspected of having BK virus-associated nephropathy and who were admitted to Namazi Hospital were enrolled for analysis between years 2010 and 2013. Blood samples were collected from each patient. The BK polyomavirus infection was diagnosed using quantitative real-time polymerase chain reaction. The BK polyomavirus -infected patient plasma samples were amplified using in-house nested polymerase chain reaction and sequenced. The contiguous alignment noncoding control region sequences were analyzed with software. Results: The BK polyomavirus infection was observed in plasma samples of 11 of 129 (8.5%) patients after kidney transplant. Sequence align-ments showed that BK polyomavirus noncoding control region sequences in all viral infected patients with BK virus-associated nephropathy showed a complete rearranged algorithm com-pared with the archetype sequences. The most prevalent noncoding control region sequences were registered in a genetic sequence database (National Institutes of Health). No association was observed between risk factors and BK polyomavirus infection. There were 3 BK polyomavirus -infected patients who simultaneously had active cytomegalovirus infection. Conclusions: Determination of the rearranged pattern of the noncoding control region sequences in BK polyomavirus isolates from plasma samples may help improve the diagnostic and therapeutic protocols against this viral infection in patients with BK virus-associated nephropathy.