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A comparative study of Merkel cell, BK and JC polyomavirus infections in renal transplant recipients and healthy subjects

https://doi.org/10.1016/j.jcv.2010.06.017Get rights and content

Abstract

Background

Merkel cell carcinoma (MCC) is a rare skin cancer associated with immunosuppression and the integration of Merkel cell polyomavirus (MCPyV) DNA into the tumor cell genome. Little is known about the natural history of MCPyV infection.

Objectives

To investigate the presence of MCPyV, BK and JC polyomaviruses in serum and urine from immunosuppressed kidney transplant patients (KTx) and a control group of normal volunteers.

Study design

Quantitative real-time PCR (q-PCR) was used to assess MCPyV, BKV and JCV viral load in urine and serum samples collected from normal donors (Group A), prospectively enrolled KTx patients (Group B) and from KTx with documented BK reactivation and/or nephropathy (Group C).

Results

Low levels of MCPyV viruria was seen in 15% of the subjects in Group A, 30% of Group B, and was not detected in Group C. No individuals in the study developed MCPyV viremia. BK viruria was seen in 5% of Group A, 30% of Group B, and 100% of Group C. Consistent with previous reports, the mean BKV urinary load was significantly higher in immunosuppressed patients compared to non-immunosuppressed controls and also higher in urine compared to serum samples.

Conclusions

Like BKV and JCV, MCPyV is likely a common infection in adult humans. Low level shedding of MCPyV in urine was similar in immunosuppressed organ transplant recipients to non-immunosuppressed subjects. However, MCPyV was not detected and JCV was infrequent in samples from KTx patients with clinical BKV reactivation.

Section snippets

Background

Merkel cell carcinoma (MCC) is an uncommon but aggressive malignant skin cancer of the elderly and immunocompromised. While rare, the incidence of MCC is increasing1 and it frequently has a poor prognosis.2 MCC occurs more frequently in organ transplant recipients and the ratio of MCC to melanoma is higher in this group than in the general population.3, 4 A novel human polyomavirus, Merkel cell polyomavirus (MCPyV), was identified recently in samples of MCC by digital transcriptome subtraction.5

Objectives

The aim of this study was to simultaneously quantify and compare MCPyV, BKV and JCV viral loads in urine and blood samples obtained from immunosuppressed KTx, KTx with documented BKV reactivation, and a control group of normal donors.

Study participants and sample collection

Urine samples were obtained at a single timepoint from 20 healthy anonymous donors (Group A), and serum (82 samples) and urine (70 samples) at monthly intervals from 20 KTx prospectively enrolled at the time of transplant (Group B) and from 5 KTx (15 urine and 15 serum samples) enrolled at the time of documented BKV reactivation in PCR screening assays performed as part of standard patient care at UCLA (Group C). All KTx gave informed consent and samples were collected in accordance with

Results

In an analysis of urine samples from 20 normal donors (Group A), MCPyV viruria was observed at low levels in three subjects (15%), with viral loads varying from 10 to 90 gc/ml. Low level BK viruria was documented in one individual (5%), while JC viruria was seen in three donors (15%) with viral loads varying from 10 to 4.5 × 104 gc/ml (Table 2 and Fig. 1).

The study of immunosuppressed patients included both prospectively enrolled kidney transplant patients (Group B) and kidney transplant patients

Discussion

Our study quantifies and compares three human polyomaviruses, MCPyV, BKV and JCV in samples from normal donors and KTx patients receiving immunosuppressive therapy. We also examined a small group of KTx who were previously identified by serum PCR as failing to control BKV. Our results indicate very low level MCPyV and JCV shedding in the urine of normal subjects (15%) and the prospectively enrolled renal transplant recipients (30%). This indicates that despite the rarity of MCC, the associated

Conflict of interest

The authors have no conflicts of interest to declare.

Acknowledgements

The authors thank Eileen Kim for technical assistance. Funding was from R21 DK077374 NIDDK to SFL.

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