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Open Access Research

Early monitoring of the human polyomavirus BK replication and sequencing analysis in a cohort of adult kidney transplant patients treated with basiliximab

Elena Anzivino1, Anna Bellizzi1, Anna Paola Mitterhofer2, Francesca Tinti2, Mario Barile2, Maria Teresa Colosimo1, Daniela Fioriti4, Monica Mischitelli15, Fernanda Chiarini1, Giancarlo Ferretti3, Gloria Taliani3 and Valeria Pietropaolo16*

Author Affiliations

1 Department of Public Health and Infectious Diseases, "Sapienza" University of Rome, Rome, Italy

2 Department of Clinical Medicine, Nephrology and Dialysis Unit, "Sapienza" University of Rome, Rome, Italy

3 Department of Infectious and Tropical Diseases, "Sapienza" University of Rome, Rome, Italy

4 National Institute for Infectious Diseases Lazzaro Spallanzani, Rome, Italy

5 Doctoral School of Oncology and Genetics, University of Siena, Siena, Italy

6 Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, Pennsylvania, USA

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Virology Journal 2011, 8:407  doi:10.1186/1743-422X-8-407

Published: 17 August 2011

Abstract

Background

Nowadays, better immunosuppressors have decreased the rates of acute rejection in kidney transplantation, but have also led to the emergence of BKV-associated nephropathy (BKVAN). Therefore, we prospectively investigated BKV load in plasma and urine samples in a cohort of kidney transplants, receiving basiliximab combined with a mycophenolate mofetil-based triple immunotherapy, to evaluate the difference between BKV replication during the first 3 months post-transplantation, characterized by the non-depleting action of basiliximab, versus the second 3 months, in which the maintenance therapy acts alone. We also performed sequencing analysis to assess whether a particular BKV subtype/subgroup or transcriptional control region (TCR) variants were present.

Methods

We monitored BK viruria and viremia by quantitative polymerase chain reaction (Q-PCR) at 12 hours (Tx), 1 (T1), 3 (T2) and 6 (T3) months post-transplantation among 60 kidney transplant patients. Sequencing analysis was performed by nested-PCR with specific primers for TCR and VP1 regions. Data were statistically analyzed using χ2 test and Student's t-test.

Results

BKV was detected at Tx in 4/60 urine and in 16/60 plasma, with median viral loads of 3,70 log GEq/mL and 3,79 log GEq/mL, respectively, followed by a significant increase of both BKV-positive transplants (32/60) and median values of viruria (5,78 log GEq/mL) and viremia (4,52 log GEq/mL) at T2. Conversely, a significantly decrease of patients with viruria and viremia (17/60) was observed at T3, together with a reduction of the median urinary and plasma viral loads (4,09 log GEq/mL and 4,00 log GEq/mL, respectively). BKV TCR sequence analysis always showed the presence of archetypal sequences, with a few single-nucleotide substitutions and one nucleotide insertion that, interestingly, were all representative of the particular subtypes/subgroups we identified by VP1 sequencing analysis: I/b-2 and IV/c-2.

Conclusions

Our results confirm previous studies indicating that BKV replication may occur during the early hours after kidney transplantation, reaches the highest incidence in the third post-transplantation month and then decreases within the sixth month, maybe due to induction therapy. Moreover, it might become clinically useful whether specific BKV subtypes or rearrangements could be linked to a particular disease state in order to detect them before BKVAN onset.

Keywords:
BKV; BKVAN; basiliximab; Q-PCR; TCR; VP1; BKV subtype/subgroup