Viral Genomic Characterization and Replication Pattern of Human Polyomaviruses in Kidney Transplant Recipients.

Lucia Signorini,Evaldo Favi,Pasquale Ferrante,Giuseppe Basile,Serena Delbue,Mariano Ferraresso,Maria Dolci,Caterina Colico,Rosalia Ticozzi

doi:10.3390/v12111280

Abstract

Human Polyomavirus (HPyV) infections are common, ranging from 60% to 100%. In kidney transplant (KTx) recipients, HPyVs have been associated with allograft nephropathy, progressive multifocal leukoencephalopathy, and skin cancer. Whether such complications are caused by viral reactivation or primary infection transmitted by the donor remains debated. This study aimed to investigate the replication pattern and genomic characterization of BK Polyomavirus (BKPyV), JC Polyomavirus (JCPyV), and Merkel Cell Polyomavirus (MCPyV) infections in KTx. Urine samples from 57 KTx donor/recipient pairs were collected immediately before organ retrieval/transplant and periodically up to post-operative day 540. Specimens were tested for the presence of BKPyV, JCPyV, and MCPyV genome by virus-specific Real-Time PCR and molecularly characterized. HPyVs genome was detected in 49.1% of donors and 77.2% of recipients. Sequences analysis revealed the archetypal strain for JCPyV, TU and Dunlop strains for BKPyV, and IIa-2 strain for MCPyV. VP1 genotyping showed a high frequency for JCPyV genotype 1 and BKPyV genotype I. Our experience demonstrates that after KTx, HPyVs genome remains stable over time with no emergence of quasi-species. HPyVs strains isolated in donor/recipient pairs are mostly identical, suggesting that viruses detected in the recipient may be transmitted by the allograft.

Highlights

Human Polyomaviruses (HPyVs) are ubiquitous DNA viruses with a reported seroprevalence in the general population ranging from 60% to 100%, depending on the series [1,2]
BK Polyomavirus (BKPyV) has been linked to Polyomavirus-associated nephropathy (PVAN), JC Polyomavirus (JCPyV) to progressive multifocal leukoencephalopathy (PML), and Merkel Cell Polyomavirus (MCPyV) to some forms of non-melanoma skin cancer [6]
The main objectives of the present study were to evaluate the prevalence of JCPyV, BKPyV, and MCPyV in the actual KTx donors and recipients pool, to investigate whether episodes of viral replication during the various post-transplant phases are due to reactivations of previously acquired latent viruses or rather primary infections transmitted by the allograft, to assess possible interactions between different HPyVs, and to further characterize clinically relevant strains and genotypes

Summary

Introduction

Human Polyomaviruses (HPyVs) are ubiquitous DNA viruses with a reported seroprevalence in the general population ranging from 60% to 100%, depending on the series [1,2]. HPyVs can start uncontrolled replication and eventually lead to cell lysis, necrosis, and irreversible tissue damage [1]. Due to their chronic exposure to powerful immunosuppressive agents, kidney transplant (KTx) recipients have a greater risk of clinically significant HPyVs infections than healthy controls [3,4]. The most relevant HPyVs detected in this particular group of patients are BK Polyomavirus (BKPyV), JC Polyomavirus (JCPyV), and Merkel Cell Polyomavirus (MCPyV) [2,4,5]. BKPyV has been linked to Polyomavirus-associated nephropathy (PVAN), JCPyV to progressive multifocal leukoencephalopathy (PML), and MCPyV to some forms of non-melanoma skin cancer [6]

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